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Background Compared with a natural process, surgically induced menopausal women have a higher bone loss rate. This study aims to evaluate early treatment with estradiol valerate on bone turnover markers after surgically induced menopause. Methods This prospective study included 41 pre and perimenopausal women who underwent hysterectomy with oophorectomy for benign gynecologic conditions. Two weeks after the operation, all participants were assessed for menopausal hormone therapy (MHT) indications. Estrogen therapy was prescribed for those who had indications and accepted treatment (hormone treatment group). The others who had no MHT indication were allocated to the no-treatment group. Serum CTX and P1NP levels at preoperative and 12 weeks postoperative were measured and set as the primary outcome. Within the same group, serum CTX and P1NP before and after surgical menopause were analyzed using Wilcoxon signed-rank test. ANCOVA was used to compare serum CTX and P1NP at 12 weeks after surgical menopause between the two groups. Spearman's rank correlation coefficient analysis analyzed the correlation between age and baseline bone turnover markers. A p-value of Results At 12 weeks after surgery, there were no significant differences in serum CTX and P1NP levels in the hormone treatment group compared to baseline. In contrast, serum CTX and P1NP levels were significantly elevated among women who did not receive hormone treatment (p-value p-value Conclusion Early estrogen administration with oral estradiol valerate could significantly suppress the high bone remodeling in surgically induced menopausal women. Trial registration Thai Clinical Trial Registry identification number TCTR20190808004, retrospective registered since 2019-08-08. http://www.thaiclinicaltrials.org/show/TCTR20190808004.

Background. The purpose was to determine the level of N-terminal of type I procollagen (PINP) and carboxy-terminal telopeptide of type I collagen (β-CTX) and their relationship in the serum of a healthy Ukrainian population of varying age and gender. Materials and methods. The study included 3,850 people aged 20–89 years (3,351 women (mean age 59.05 ± 13.89 years) and 499 men (49.17 ± 15.8 years). All participants were divided by age based on the gerontological age classification: young age 20–44 yrs, middle age 45–59 yrs, elderly 60–74 yrs, and old 75–89 yrs, and between 7 groups by decades: from 20 to 89. β-CTX and serum PINP concentrations were determined by electrochemiluminescence immunoassay ECLIA on a Cobas E411 analyzer. Results. We have detected a significant effect of age on serum β-CTX and PINP variability in men (F = 6.64, p, Целью исследования является определение уровня N-терминального пропептида проколлагена I типа (PINP) и карбокситерминального телопептида коллагена I типа (β-CTX) и их взаимосвязи в сыворотке крови у здорового населения Украины разного возраста и пола. Материалы и методы. В исследование было включено 3850 человек в возрасте 20–89 лет (3351 женщина (средний возраст 59,05 ± 13,89 года) и 499 мужчин (49,17 ± 15,8 года)). Всех участников распределили по возрасту в соответствии с геронтологической классификацией на 4 группы: молодой возраст — 20–44 года, средний — 45–59 лет, пожилой — 60–74 года и старческий возраст — 75–89 лет, а также на 7 групп по десятилетиям: от 20 до 89 лет. Концентрацию β-CTX и PINP в сыворотке крови определяли методом электрохемилюминесцентного иммуно­анализа ECLIA на анализаторе cobas e 411. Результаты. Выявлено достоверное влияние возраста на вариабельность β-CTX и PINP у мужчин (F = 6,64, р < 0,001, и F = 4,93, р < 0,001) и женщин (F = 16,17, р < 0,001, и F = 10,46, р < 0,001). У женщин по критерию Шеффе обнаружили достоверно более высокий уровень β-CTX в группе 80–89 лет по сравнению с группами 20–29 лет (р = 0,01), 30–39 лет (р < 0,001), 40–49 лет (р < 0,001), 50–59 лет (0,52 ± 0,27, р = 0,002), 60–69 лет (р = 0,001) и 70–79 лет (р = 0,04). Показатели PINP в группе 80–89 лет также были достоверно выше в сравнении с группами 30–39 лет (р < 0,001), 40–49 лет (р < 0,001), 50–59 лет (р = 0,009), 60–69 лет (р = 0,002) и 70–79 лет (р = 0,02). У мужчин обнаружили достоверное снижение концентрации β-CTX в группах: 30–39 лет (р = 0,02), 40–49 лет (р < 0,001), 50–59 лет (р = 0,01) и 60–69 лет (р = 0,001) в сравнении с группой 20–29 лет. Уровень PINP был достоверно ниже в группах 40–49 лет (р < 0,001) и 50–59 лет (р = 0,03) в сравнении с группой 20–29 лет. По результатам исследования, коэффициент корреляции между показателями концентрации PINP и β-CTX изменяется в зависимости от возраста и пола. Самые высокие коэффициенты корреляции среди обоих полов наблюдались в возрастных группах 40–49 (женщины: r = 0,74; мужчины: r = 0,64) и 50–59 (женщины: r = 0,74; мужчины: r = 0,66) лет; низкие коэффициенты корреляции у женщин наблюдались в возрастной группе 20–29 (r = 0,63) и 70–79 (r = 0,65) лет; у мужчин (r = 0,53) в возрасте 20–29 и 70–79 лет. Выводы. Выявлено достоверное влияние возраста на вариабельность β-CTX и PINP в сыворотке крови у мужчин и женщин. Наиболее высокая корреляционная связь между концентрациями β-CTX и PINP наблюдалась в группах 40–49 и 50–59 лет среди обоих полов. Полученные результаты могут быть использованы у практически здоровых мужчин и женщин Украины как референтные, а в будущем будут необходимыми для изучения метаболизма костной ткани при вторичном остеопорозе и его осложнениях., Метою дослідження є визначення рівня N-термінального пропептиду проколагену I типу (PINP) і карбокситермінального телопептиду колагену I типу (β-CTX) та їх взаємозв’язку в сироватці крові в здорового населення України різного віку та статі. Матеріали та методи. У дослідження було включено 3850 осіб віком 20–89 років (3351 жінка (середній вік 59,05 ± 13,89 року) та 499 чоловіків (49,17 ± 15,8 року)). Усіх учасників розподілили за віком відповідно до геронтологічної класифікації на 4 групи: молодий вік — 20–44 роки, середній — 45–59 років, літній — 60–74 роки та старечий вік — 75–89 років, а також на 7 груп за десятиріччями: від 20 до 89 років. Концентрацію β-CTX та PINP у сироватці крові визначали методом електрохемілюмінесцентного імуноаналізу ECLIA на аналізаторі cobas e 411. Результати. Виявлено вірогідний вплив віку на варіабельність β-CTX та PINP у чоловіків (F = 6,64, р < 0,001, та F = 4,93, р < 0,001) і жінок (F = 16,17, р < 0,001, та F = 10,46, р < 0,001). У жінок за критерієм Шеффе виявили вірогідно вищий рівень β-CTX у групі 80–89 років порівняно із групами 20–29 років (р = 0,01), 30–39 років (р < 0,001), 40–49 років (р < 0,001), 50–59 років (0,52 ± 0,27, р = 0,002), 60–69 років (р = 0,001) та 70–79 років (р = 0,04). Показники PINP у групі 80–89 років також були вірогідно вищими порівняно із групами 30–39 років (р < 0,001), 40–49 років (р < 0,001), 50–59 років (р = 0,009), 60–69 років (р = 0,002) та 70–79 років (р = 0,02). У чоловіків ви­явили вірогідне зниження концентрації β-CTX у групах: 30–39 років (р = 0,02), 40–49 років (р < 0,001), 50–59 років (р = 0,01) та 60–69 років (р = 0,001) порівняно із групою 20–29 років. Рівень PINP був вірогідно нижчим у групах 40–49 років (р < 0,001) та 50–59 років (р = 0,03) порівняно із групою 20–29 років. За результатами дослідження, коефіцієнт кореляції між показниками концентрації PINP та β-CTX змінюється залежно від віку та статі. Найвищі коефіцієнти кореляції серед обох статей спостерігалися у вікових групах 40–49 (жінки: r = 0,74; чоловіки: r = 0,64) та 50–59 (жінки: r = 0,74; чоловіки: r = 0,66) років; найнижчі коефіцієнти кореляції в жінок спостерігалися у віковій групі 20–29 (r = 0,63) та 70–79 (r = 0,65) років; у чоловіків (r = 0,53) віком 20–29 та 70–79 років. Висновки. Виявлено вірогідний вплив віку на варіабельність β-CTX та PINP у сироватці крові в чоловіків і жінок. Найвищий зв’язок між концентраціями β-CTX та PINP за коефіцієнтом кореляції спостерігався в групах 40–49 та 50–59 років серед обох статей. Отримані результати можуть бути використані в практично здорових чоловіків і жінок України як референтні, а в майбутньому будуть необхідними для вивчення метаболізму кісткової тканини при вторинному остеопорозі та його ускладненнях.

PURPOSE: Low bone mineral density (BMD) and fractures are a major concern in the female population and preventative strategies are needed. Whether team sports participation may reduce age-related bone loss in elderly women is still uncertain.METHODS: One hundred and thirty healthy, non-smoking women participated in this cross-sectional study, i.e., elderly (60-80 years) team handball players (EH, n = 35), elderly untrained controls (EC, n = 35), young (18-30 years) elite football players (YF, n = 30) and young untrained controls (YC, n = 30). A whole-body and two regional dual-energy X-ray absorptiometry (DXA) scans were performed to evaluate BMD and a blood sample was collected for measurement of bone turnover markers (BTMs).RESULTS: EH had higher BMD in all regions of the lumbar spine, except for L1, compared to EC (8-10%), and higher BMD in the femoral Ward's triangle (9%) and trochanter (7%) of the left leg. Furthermore, EH had higher mean leg BMD (8%) and whole-body BMD (5%) than EC. EH and YC had similar BMD in femoral trochanter, L1-L4 and mean leg despite an age difference of ~ 40 years. YF had higher BMD in all regions of the proximal femur (18-29%) and lumbar spine (12-16%) compared to YC, as well as higher mean leg BMD (20%) and whole-body BMD (13%). Sclerostin was 14% lower in EH compared to EC. YF showed higher PINP (98%), osteocalcin (57%), and CTX (83%) compared to YC.CONCLUSION: Lifelong team handball training and elite football training are associated with superior bone mineralization and changed bone turnover in elderly and young women.

Zelin Li,1,2 Xian Yu,2 Luping Ren,2 Zi Wang,3 Fei Wang,1,2 Yujiao Jia,1,2 Shuchun Chen1,2,4 1Graduate School of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Infectious Diseases, Shanghai Fourth People’ s Hospital, Shanghai, People’s Republic of China; 4Hebei Key Laboratory of Metabolic Diseases, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shuchun ChenDepartment of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaTel +86 31185988406Fax +86 31185988406Email chenshuc2014@163.comPurpose: The aim of this study was to investigate whether low total triiodothyronine (TT3) could affect bone turnover in patients with type 2 diabetes mellitus (T2DM).Materials and Methods: This is a cross-sectional study that recruited 577 patients with T2DM, 141 patients formed the low TT3 group (TT3< 1.30nmol/L) and 436 patients formed the control group (TT3≥ 1.30nmol/L), and the low TT3 group was further subdivided into four groups based on the TT3 level. To investigate whether TT3 level is associated with poor glycemic control, all participants were divided into high glycosylated hemoglobin (HbA1c) group and low HbA1c group using HbA1c 10.5% as the boundary.Results: The levels of OC and PINP were significantly lower in the low TT3 group compared with the control group (P < 0.05). TT3 positively correlated with OC and PINP (r = 0.219, P = 0.009; r = 0.208, P = 0.019) in the low TT3 group, and this positive correlation still existed after adjusting for other factors in multilinear regression analysis. Next, we want to find a cut-off point to prevent osteoporosis, we divided the patients in the low TT3 group into four groups based on the TT3 level, the levels of OC and PINP were significantly lower in the TT3 < 1.00 nmol/L group than in the TT3 ≥ 1.00 nmol/L groups.Conclusion: In patients with T2DM, low TT3 levels are associated with impaired bone formation. What’s more, bone formation was significantly impaired when TT3 was < 1.00 nmol/L.Keywords: bone turnover markers, low TT3 level, thyroid hormones, type 2 diabetes mellitus

ObjectiveAn increased prevalence of vertebral fractures (VFs) has been reported in previous studies. The aim of this study was to evaluate the association between bone mineral density (BMD), bone turnover markers, serum sclerostin levels, and vertebral fractures (VFs) in acromegaly patients. We also evaluated the effects of gonadal status, disease activity, treatment modality, age, sex, and body mass index (BMI) on skeletal endpoints.DesignCase-control study.Patients and measurementsSeventy acromegaly patients (M/F:36/34, mean age 45,5±11,9 years) and 70 controls (M/F:31/39; mean age 45.66±11.9 years) were included. VFs, BMD, calcium metabolism, markers of bone turnover, and sclerostin levels were evaluated. BMD was measured by dual-energy X-ray absorptiometry (Hologic QDR 4500). Conventional lateral radiography of the spine was performed and the Genant method was used for the assessment of fractures of T4–L5 vertebrae.ResultsThe prevalence of vertebral fractures was higher in acromegalic patients as compared with the control group (72.9% vs. 20%; p

Blood flow restriction may augment the skeletal response to whole-body vibration. This study used a randomised, crossover design to investigate the acute response of serum sclerostin and bone turnover biomarkers to whole-body vibration with blood flow restriction. Ten healthy males (mean±standard deviation; age: 27±8 years) completed two experimental conditions separated by 7 days: (i) whole-body vibration (10 1-minute bouts of whole-body vibration with 30 s recovery) or (ii) whole-body vibration with lower-body blood flow restriction (10 cycles of 110 mmHg inflation with 30 s deflation during recovery). Fasting blood samples were obtained immediately before and immediately after exercise, then 1 hour, and 24 hours after exercise. Serum samples were analysed for sclerostin, cross-linked C-terminal telopeptide of type I collagen, and bone-specific alkaline phosphatase. There was a significant time × condition interaction for bone-specific alkaline phosphatase (p=0.003); bone-specific alkaline phosphatase values at 24 hours post-exercise were significantly higher following whole-body vibration compared to combined whole-body vibration and blood flow restriction (p=0.028). No significant time × condition interaction occurred for any other outcome measure (p0.05). These findings suggest that a single session of whole-body vibration combined with blood flow restriction does not significantly affect serum sclerostin or bone turnover biomarkers.Blood flow restriction may augment the skeletal response to whole-body vibration. This study used a randomised, crossover design to investigate the acute response of serum sclerostin and bone turnover biomarkers to whole-body vibration with blood flow restriction. Ten healthy males (mean±standard deviation; age: 27±8 years) completed two experimental conditions separated by 7 days: (i) whole-body vibration (10 1-minute bouts of whole-body vibration with 30 s recovery) or (ii) whole-body vibration with lower-body blood flow restriction (10 cycles of 110 mmHg inflation with 30 s deflation during recovery). Fasting blood samples were obtained immediately before and immediately after exercise, then 1 hour, and 24 hours after exercise. Serum samples were analysed for sclerostin, cross-linked C-terminal telopeptide of type I collagen, and bone-specific alkaline phosphatase. There was a significant time × condition interaction for bone-specific alkaline phosphatase (p=0.003); bone-specific alkaline phosphatase values at 24 hours post-exercise were significantly higher following whole-body vibration compared to combined whole-body vibration and blood flow restriction (p=0.028). No significant time × condition interaction occurred for any other outcome measure (p0.05). These findings suggest that a single session of whole-body vibration combined with blood flow restriction does not significantly affect serum sclerostin or bone turnover biomarkers.

Procollagen type I N-propeptide (PINP) and the C-terminal telopeptide of type I collagen (β-CTX) in blood have been designated as reference bone turnover markers in osteoporosis by the International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The IFCC Committee on Bone Metabolism (C-BM) has examined current commercial assays and performed a multicentre study to examine the agreement between assays for PINP and β-CTX in serum and plasma. The results of these studies will inform our work towards the harmonization of PINP assays and the standardization of β-CTX assays in blood, with the development of common calibrators and reference measurement procedures in collaboration with the reagent manufacturing industry. Successful achievement of these goals will help develop universally acceptable practice guidelines for the management of osteoporosis with the inclusion of common reference intervals and treatment targets for PINP and β-CTX.

Background Biochemical bone turnover markers are useful tools to assess bone remodeling. C-terminal telopeptide of type I collagen (ß-CTX) has been recommended as a reference marker for bone resorption in research studies. Methods We describe the results of a multicenter study for routine clinical laboratory assays for ß-CTX in serum and plasma. Four centers (Athens GR, Copenhagen DK, Liege BE and Sheffield UK) collected serum and plasma (EDTA) samples from 796 patients presenting to osteoporosis clinics. Specimens were analyzed in duplicate with each of the available routine clinical laboratory methods according to the manufacturers’ instructions. Passing-Bablok regressions, Bland–Altman plots, V-shape evaluation method, and Concordance correlation coefficient for ß-CTX values between serum and plasma specimens and between methods were used to determine the agreement between results. A generalized linear model was employed to identify possible variables that affected the relationship between the methods. Two pools of serum were finally prepared and sent to the four centers to be measured in 5-plicates on 5 consecutive days with the different methods. Results We identified significant variations between methods and between centers although comparison results were generally more consistent in plasma compared to serum. We developed univariate linear regression equations to predict Roche Elecsys®, IDS-iSYS, or IDS ELISA ß-CTX results from any other assay and a multivariable model including the site of analysis, the age, and weight of the patient. The coefficients of determination (R2) increased from approximately 0.80 in the univariate model to approximately 0.90 in the multivariable one, with the site of analysis being the major contributing factor. Results observed on the pools also suggest that long-term storage could explain the difference observed with the different methods on serum. Conclusion Our results show large within- and between-assay variation for ß-CTX measurement, particularly in serum. Stability of the analyte could be one of the explanations. More studies should be undertaken to overcome this problem. Until harmonization is achieved, we recommend measuring ß-CTX by the same assay on EDTA plasma, especially for research purposes in large pharmacological trials where samples can be stored for long periods before they are assayed.

Background: This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmeno pausal women with osteoporosis. Methods: Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤-2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months. Results: At month 6, the difference in the least square (LS) mean percent change from baseline in lumbar spine BMD (primary effi cacy endpoint) between the romosozumab (9.5%) and placebo (-0.1%) groups was significant (9.6%; 95% confidence interval, 7.6 to 11.5; P

Discontinuation of denosumab treatment is associated with rapid bone loss that could be prevented in many patients by zoledronate (ZOL) infusion given 6 months after the last denosumab injection. The effects, however, of zoledronate administration at a later time point are unknown. We aimed to compare the 1-year effect of ZOL infusion given 6 versus 18 months following the last Dmab injection. In this extension of a previously reported 2-year randomized clinical trial, we included initially treatment-naive postmenopausal women, who became osteopenic after approximately 2.5 years of denosumab therapy, and were subjected to a single ZOL infusion at 6 months (early-ZOL, n = 27) versus 18 months (late-ZOL, n = 15) after the last Dmab injection. Annual changes in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD), and markers of bone turnover (P1NP, CTx) at 6 and 12 months following ZOL infusion were assessed. LS BMD was maintained in both early-ZOL (+ 1.7%) and late-ZOL (+ 1.8%) infusion with no difference between groups (p = 0.949). FN BMD was maintained in early-ZOL (+ 0.1%) and increased in late-ZOL (+ 3.4%) infusion with no difference between groups (p = 0.182). Compared to 6 months after last Dmab injection, the overall LS BMD change of the late-ZOL group (- 3.5%) was significantly different (p = 0.007) from that of the early-ZOL group (+ 1.7%). P1NP and CTx gradually increased in the early-ZOL group, while profoundly decreased and remained suppressed in the late-ZOL infusion. A ZOL infusion 18 months following the last Dmab injection is still useful in terms of BMD maintenance and BTM suppression. However, there is no clear clinical benefit compared to the early infusion, while any theoretical advantage is counterbalanced from the expected bone loss, especially at the LS, and the risk of rebound-associated fractures. Trial Registration: NCT02499237; July 16, 2015

Background In this retrospective study, we studied the impact of educational osteoporosis program on the rates of bone mineral density (BMD) assessment and bone turnover markers (BTM) and drug medications in the patients with hip fracture. Methods This retrospective research enrolled 651 patients aged ≥50 years who experienced hip fractures from January 2013 to December 2015. We recorded whether patients had received BMD assessment, BTM measurement, and anti-osteoporosis therapy during the period of hospitalization. Orthopedic surgeons were classified into the trained group and the untrained group. The rates of BMD assessment, BTM measurement, and anti-osteoporosis medications in the patients with hip fracture were compared between the trained group and the untrained group. Results BMD assessment was performed in 109/220 patients in the trained group and 142/431 patients in the untrained group. BTM measurements were performed in 130 patients in the trained group and 124 patients in the untrained group. Forty eight patients in the trained group and 63 patients in the untrained group received bisphosphonate medications. Conclusions Although the rates of BMD assessment, BTM measurement, and bisphosphonate use in the patients after hip fractures are still insufficient, education programs help to improve the situation.

Denosumab discontinuation is associated with a rapid increase in bone resorption and a decrease in bone mineral density. Spontaneous vertebral fractures may occur as a side effect of the rebound of bone resorption. Cases of rebound-linked hypercalcemia have also been described, moderate in women with osteoporosis and breast cancer and severe in children receiving oncological doses of denosumab. We report the case of an adult woman with primary hyperparathyroidism and moderate hypercalcemia, treated with denosumab for osteoporosis, who developed severe hypercalcemia and spontaneous vertebral fractures (SVFs) after denosumab discontinuation. An 86-year-old woman with densitometric osteoporosis was treated for 3 years with 60 mg of subcutaneous denosumab every 6 months. She was known to have primary hyperparathyroidism, with a serum albumin-corrected calcium of 2.82 mmol/l (NV 2.15-2.5) at the end of denosumab effect. Nine months after the last denosumab injection, she was hospitalized due to worsening overall health. Clinical evaluation revealed severe hypercalcemia (calcium 3.35 mmol/l). Very high values of bone turnover markers (BTMs) suggested a rebound effect due to denosumab discontinuation. An X-ray showed multiple new SVFs. After injection of denosumab 60 mg, serum calcium rapidly decreased and BTMs were dramatically reduced. A surgical approach by minimally invasive parathyroidectomy allowed for definite resolution of hyperparathyroidism and hypercalcemia. This case suggests that hypercalcemia can be a side consequence of denosumab discontinuation, which can become severe when other causes of hypercalcemia, such as primary hyperparathyroidism, are present.

Aim of the work: To assess the bone turnover markers and bone mineral density (BMD) in ankylosing spondylitis (AS) patients and to evaluate their association with clinical variables. Patients and methods: Forty-seven AS patients were compared with 47 matched control. Clinical features and inflammatory parameters were assessed. C-terminal telopeptide fragments of type I collagen (CTX), alkaline phosphatases (ALP), N-terminal propeptide of type I procollagen (PINP) serum levels, and BMD of the lumbar spine and femoral neck were evaluated. The Bath AS disease activity and functional indices (BASDAI and BASFI) were assessed. Results: Mean serum levels of C-reactive protein, ALP and CTX were higher in AS patients than control (p = 0.001, p = 0.001 and p = 0.027 respectively). Osteopenia and osteoporosis were significantly more frequent in AS patients (57.4%) than control (21.3%) (p

Background The prognosis is very poor for lung cancer patients with bone metastasis. Unfortunately, a suitable method has yet to become available for the early diagnosis of bone metastasis in lung cancer patients. The present work describes an attempt to develop a novel model for the early identification of lung cancer patients with bone metastasis risk. Methods As the test group, 205 primary lung cancer patients were recruited, of which 127 patients had bone metastasis; the other 78 patients without bone metastasis were set as the negative control. Additionally, 106 healthy volunteers were enrolled as the normal control. Serum levels of several cytokines in the bone microenvironment (CaN, OPG, PTHrP, and IL-6) and bone turnover markers (tP1NP, β-CTx) were detected in all samples by ECLIA or ELISA assay. Receiver operating characteristic (ROC) curves and multivariate analyses were performed to evaluate diagnostic abilities and to assess the attributable risk of bone metastasis for each of these indicators; the diagnostic model was established via logistic regression analysis. The prospective validation group consisted of 44 patients with stage IV primary lung cancer on whom a follow-up of at least 2 years was conducted, during which serum bone biochemical marker concentrations were monitored. Results The serological molecular model for the diagnosis of bone metastasis was logit (p). ROC analysis showed that when logit (p) > 0.452, the area under curve of the model was 0.939 (sensitivity: 85.8%, specificity: 89.7%). Model validation demonstrated accuracy with a high degree of consistency (specificity: 85.7%, specificity: 87.5%, Kappa: 0.770). The average predictive time for bone metastasis occurrence of the model was 9.46 months earlier than that of the bone scan diagnosis. Serum OPG, PTHrP, tP1NP, β-CTx, and the diagnostic model logit (p) were all positively correlated with bone metastasis progression (P Conclusions This diagnostic model has the potential to be a simple, non-invasive, and sensitive tool for diagnosing the occurrence and monitoring the progression of bone metastasis in patients with lung cancer.

Objective With the aging of society, both osteoporosis and fatty liver disease (FLD) are becoming important issues. However, the relationship between osteoporosis and FLD remains controversial. We investigated the association between bone metabolism and FLD in a Japanese community in a cross-sectional study. Methods A total of 1,020 participants were enrolled in a health survey. FLD was diagnosed by ultrasonography. Bone metabolism was evaluated based on bone mineral density (BMD), which was assessed using dual-energy X-ray absorptiometry, and with the bone formation index (total type I procollagen N-terminal propeptide/bone-alkaline phosphatase ratio; P1NP/BAP ratio) and the bone resorption index (crosslinked N-telopeptide of type I collagen/tartrate-resistant acid phosphatase-5b ratio; NTx/TRACP-5b ratio) calculated from serum bone turnover markers. Results The BMD (percentage of the young adult mean) was the same level in both male and female participants with and without FLD. Both men and women showed an age-dependent decrease in their bone formation index and bone resorption index values. Men of ≥70 years of age and women of 60-69 years of age with FLD had significantly lower bone formation index values and higher bone resorption index values. However, similar findings were not seen in women of ≥70 years of age. Conclusion Although the BMD levels were the same, regardless of the presence or absence of FLD, elderly participants with FLD showed decreased bone formation and increased bone resorption, with sex differences. Because our results suggest that FLD in elderly individuals is detrimental for bone metabolism, and that it leads to bone loss and osteoporosis, further studies using a cohort population are warranted.

Background Although unhealthy alcohol use and low bone density are prevalent among people living with HIV (PLWH), it is not clear whether alcohol use is associated with bone turnover markers (BTMs), and if so, at what quantity and frequency. The study objective was to examine the association between alcohol and BTMs in PLWH with substance use disorder. Methods We studied a prospective cohort recruited from 2 HIV clinics who met criteria for DSM‐IV substance dependence or reported ever injection drug use. Outcomes were BTM of (i) bone formation (serum procollagen type 1 N‐terminal propeptide [P1NP]) and (ii) bone resorption (serum C‐telopeptide type 1 collagen [CTx]). Alcohol consumption measures included (i) mean number of drinks/d (Timeline Follow‐Back [TLFB]) (primary predictor), (ii) any alcohol use on ≥20 of the past 30 days, and phosphatidylethanol (PEth), a biomarker of recent alcohol consumption. Linear regression analysis examined associations between (i) each alcohol measure and each BTM and (ii) change in alcohol and change in BTM over 12 months. Results Among 198 participants, baseline characteristics were as follows: The median age was 50 years; 38% were female; 93% were prescribed antiretroviral medications; 13% had ≥20 drinking days/month; mean drinks/day was 1.93 (SD 3.89); change in mean drinks/day was −0.42 (SD 4.18); mean P1NP was 73.1 ng/ml (SD 34.5); and mean CTx was 0.36 ng/ml (SD 0.34). Higher drinks/day was significantly associated with lower P1NP (slope −1.09 ng/ml; 95% confidence interval [CI] −1.94, −0.23, per each additional drink). On average, those who drank on ≥ 20 days/month had lower P1NP (−15.45 ng/ml; 95% CI: −26.23, −4.67) than those who did not. Similarly, PEth level ≥ 8ng/ml was associated with lower P1NP. An increase in drinks/d was associated with a decrease in P1NP nonsignificantly (−1.14; 95% CI: −2.40, +0.12; p = 0.08, per each additional drink). No significant associations were detected between either alcohol measure and CTx. Conclusions In this sample of PLWH with substance use disorder, greater alcohol consumption was associated with lower serum levels of bone formation markers., We examined whether alcohol consumption was associated with serum bone turnover markers in a sample of adults with HIV infection and a substance use disorder. Alcohol exposure was examined with three self‐report measures of past month alcohol quantity/frequency as well as phosphatidylethanol (PEth) level, a biomarker of recent alcohol consumption. All alcohol consumption measures were associated with lower levels of a bone formation marker (P!NP) but not with C‐telopeptide, a marker of bone resorption. Vitamin D deficiency was not a mediator in these associations.

Objective To investigate the clinical significance of the detection of bone mineral density (BMD) and bone turnover markers (BTM) in older women with osteoporosis, and to compare their predictive power for osteoporotic fractures (OF). Methods In this retrospective study, 96 patients with OF and 107 patients with osteoporosis who were hospitalized in the Department of Orthopedics at the First Affiliated Hospital of Chengdu Medical College were examined from October 2017 to February 2019. All selected patients were divided into either the fracture group (96 cases, 47.3%) or the non‐fracture group (107 cases, 52.7%). BMD was measured by dual‐energy X‐ray absorptiometry (DXA). BTM were detected by electrochemical luminescence: aminoterminal propeptide of type I procollagen (PINP), β‐cross‐linked C‐telopeptide of type I collagen (β‐CTX), and molecular fragment of osteocalcin N terminal (N‐MID). Bone metabolism‐related indicators were detected, including alkaline phosphatase (ALP), calcium (Ca), and phosphorus (P). Independent‐samples t‐tests were used to compare the measurement data between the two groups, one‐way ANOVA to compare the gaps between groups, and binary logistic regression to analyze the correlation of BMD and BTM with OF. Results There were no significant differences in age, weight, height, body mass index, age, and time of menopause between the two groups. There were a total of 71 cases (35.0%) in group A (60–70 years), 80 cases (39.4%) in group B (71–80 years), and 52 cases (25.6%) in group C (81–90 years). The fracture group was compared with the non‐fracture group for BMD in the lumbar (0.75 ± 0.05 vs 0.88 ± 0.13, 0.75 ± 0.16 vs 0.87 ± 0.09, 0.74 ± 0.21 vs 0.87 ± 0.12 g/cm2; P 0.05). Binary logistic regression analysis showed that for BMD in the lumbar and hip, β‐CTX and OF were significantly correlated (respectively, odds ratio [OR] = −4.182, 95% confidence interval [CI] 1.672–3.448; OR = 6.929, 95% CI 2.586–12.106; OR = 7.572, 95% CI 1.441–3.059), and the differences were statistically significant. PINP and N‐MID were correlated with OF (respectively, OR = 4.213, 95% CI 0.978–1.005; OR = 2.510, 95% CI 1.070–1.134, P > 0.05), the difference was not statistically significant. Conclusion Osteoporotic older women, with lower bone density and higher β‐CTX, are more likely to incur OF. β‐CTX is better than BMD at predicting OF and can help in its management and in implementing interventions in high‐risk populations.

Study design Prospective observational study. Purpose To evaluate bone turnover markers (BTMs) in individuals with acute spinal cord injury (SCI) and to compare the results with those of healthy controls and postmenopausal females. Overview of literature SCI significantly impacts bone health. Change in bone mineral density appears 6 months after SCI and rapid bone loss during the acute phase is often underestimated, resulting in osteoporosis and a high risk of sublesional fractures. However, few studies have evaluated BTMs in the Indian SCI population. Despite a high risk of fracture, there are no guidelines for the diagnosis, monitoring, and management of SCI-induced osteoporosis. Methods Twenty patients within 1 month of traumatic SCI who had been admitted to a tertiary care rehabilitation center were included in this study. Serum BTMs, C telopeptide (CTX) as a bone resorption marker, and osteocalcin as a bone formation marker, were serially measured at baseline, and 3 and 6 months after SCI. BTMs of SCI patients were compared with those of a control group of age-matched healthy males, premenopausal females, and a vulnerable group of postmenopausal females. Results BTMs were significantly elevated in patients with SCI, with maximum levels observed at the 3rd month of injury. At baseline, the bone resorption marker CTX was approximately 3 times higher in SCI patients than in the control male population and premenopausal females, and about double that of postmenopausal females. The rise in the bone formation marker was marginal in comparison to that of the bone resorption marker. BTMs were persistently elevated and did not reach the normative range until the 6th month of SCI. Conclusions Raised bone resorption markers in comparison to bone formation markers indicate hyper-resorption-related bone loss following acute SCI. Markedly elevated bone resorption markers in the SCI population, compared with those in control and vulnerable groups, emphasize the need for early bone health monitoring and management.

Context Numerous studies have demonstrated detrimental skeletal consequences following bariatric surgery. Methods A working group of the European Calcified Tissue Society (ECTS) performed an updated review of existing literature on changes of bone turnover markers (BTMs), bone mineral density (BMD), and fracture risk following bariatric surgery and provided advice on management based on expert opinion. Literature review Based on observational studies, bariatric surgery is associated with a 21–44% higher risk of all fractures. Fracture risk is time-dependent and increases approximately 3 years after bariatric surgery. The bariatric procedures that have a malabsorptive component (including Roux-en-Y Gastric bypass (RYGB) and biliopancreatic diversion (BPD)) have clearly been associated with the highest risk of fracture. The extent of high-turnover bone loss suggests a severe skeletal insult. This is associated with diminished bone strength and compromised microarchitecture. RYGB was the most performed bariatric procedure worldwide until very recently, when sleeve gastrectomy (SG) became more prominent. There is growing evidence that RYGB is associated with greater reduction in BMD, greater increase in BTMs, and higher risk of fractures compared with SG but RCTs on optimal management are still lacking. Expert opinion In all patients, it is mandatory to treat vitamin D deficiency, to achieve adequate daily calcium and protein intake and to promote physical activity before and following bariatric surgery. In post-menopausal women and men older than 50 years, osteoporosis treatment would be reasonable in the presence of any of the following criteria: i) history of recent fragility fracture after 40 years of age, ii) BMD T-score ≤ −2 at hip or spine, iii) FRAX score with femoral neck BMD exceeding 20% for the 10-year major osteoporotic fracture probability or exceeding 3% for hip fracture. Zoledronate as first choice should be preferred due to intolerance of oral formulations and malabsorption. Zoledronate should be used with caution due to hypocemia risk. It is recommended to ensure adequate 25-OH vitamin D level and calcium supplementation before administering zoledronate. Conclusions The bariatric procedures that have a malabsorptive component have been associated with the highest turnover bone loss and risk of fracture. There is a knowledge gap on osteoporosis treatment in patients undergoing bariatric surgery. More research is necessary to direct and support guidelines.

Objectives: To perform a correlation analysis of serum 25-hydroxy Vitamin-D[25-OH-D], bone turnover markers (BTMs), and bone mineral density (BMD) in patients with gestational diabetes mellitus (GDM) during mid- and late pregnancy and state the significance of these factors for guiding clinical prevention and control of GDM. Methods: This study involved 100 pregnant women with singleton pregnancies who visited our obstetrics and gynecology department, Baoding First Central Hospital, during January 2019 and December 2020. All participants had received more than five prenatal checkups and were assigned to a GDM group and a normal group according to the presence of GDM during the mid-pregnancy period. Serum 25-OH-D, BMD, and bone turnover markers (BTMs) were measured to analyze the differences between the two groups and observe possible correlations among these factors. Results: According to the examination results, GDM occurred in 31 (31%) participants, and the rest 69 (69%) were free of GDM during mid-pregnancy. No significant differences were observed between the two groups in basic clinical data and the serum levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) (p>0.05), whereas the fasting blood glucose (FBG) level in the GDM group was significantly higher than in the normal group (p

Background Osteosarcopenia is referred to as co-incidence of osteoporosis/osteopenia and sarcopenia which is defined as a geriatric syndrome with a significant prevalence that increases morbidity and mortality. There are some relevant factors that can show an increased risk of incidence of osteosarcopenia. Aim We aimed to consider the association of bone turnover markers such as Osteocalcin (OC), C-terminal cross-linked telopeptide (CTX), Tartrate Resistant acid Phosphatase (TRAP), Bone Alkaline Phosphatase (BALP) and also other factors like vitamin D, calcium, phosphorous, and ALP with osteosarcopenia in elderly. Methods We carried out a cross-sectional study on a random sample including 400 elder participants of Bushehr Elderly Health (BEH) study, in Iran. Osteopenia/ osteoporosis was defined as a T-score ≤ -1.0 standard deviation below the mean values of a young healthy adult. We defined sarcopenia as low muscle strength (handgrip strength2 for male and 2 for female]. Osteosarcopenia was considered as the presence of both osteopenia/osteoporosis and sarcopenia. We estimated the age-standardized prevalence of osteosarcopenia for men and women, separately. We used multivariable logistic regression to address the factors associated with osteosarcopenia. Results The results showed that there was a statistically significant difference in OC), CTX, TRAP were between the osteosarcopenia (-) and osteosarcopenia (+) groups. No statistically significant difference was observed in BALP, vitamin D, calcium, phosphorous, and ALP between the compared groups. In the multivariable logistic regression model, OC and CTX were associated with increased likelihood of osteosarcopenia [adjusted OR= 1.023(1.002-1.045 for OC, 4.363(1.389-15.474 for CTX)]. Furthermore, TRAP increases the odds of osteosarcopenia in crude model [OR= 1.333 (1.070- 1.660)]. Conclusions We observed the association between bone turnover markers particularly OC, CTX and osteosarcopenia. Given the rapid growth of the aging population, we should focus on geriatric diseases such as musculoskeletal disorders. Bone turnover markers maybe improve the early diagnosis, screening and assess the response to therapies in people with osteosarcopenia.

Ran Li,1,2,&ast; Xiaoyi Zhu,1,2,&ast; Mengxi Zhang,1,2,&ast; Guannan Zong,1,2 Keqin Zhang1,2 1Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China; 2Institute of Osteoporosis and Metabolic Bone Diseases, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Keqin ZhangDepartment of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, No. 389, Xincun Road, Shanghai, 200065, People’s Republic of ChinaTel +86 21-66112032Email keqzhang2018@163.comBackground: It has been reported that serum periostin levels are significantly higher in postmenopausal patients with osteoporotic fractures. Nonetheless, the levels of serum periostin in postmenopausal women with different bone mass remain unclear.Purpose: The objective of the study was to identify the levels of serum periostin in Chinese postmenopausal women with different bone mass, and the correlations between the periostin levels and the classical bone turnover markers (BTMs), and bone mineral densities (BMDs) at different sites.Patients and Methods: This study enrolled 331 Chinese postmenopausal women in Shanghai; their clinical features were collected; their levels of serum periostin and traditional BTMs were measured by ELISA or the fully automated immunoassay analyzer; their BMDs at different sites were measured by dual-energy X-ray absorptiometry (DXA).Results: According to the T-value of bone mineral density (BMD), these postmenopausal women were divided into normal group (n=84), osteopenia group (n=126) and osteoporosis group (n=121). There was no significant difference in the serum periostin levels among the above three groups of subjects. In addition, Spearman correlation analysis also revealed that no correlation was observed between the value of serum periostin and those of traditional BTMs, and BMDs at different sites, respectively. The values of traditional BTMs were negatively correlated with those of BMDs at all measured sites. Furthermore, the receiver-operating characteristic (ROC) curves analysis indicated that among the periostin and traditional BTMs mentioned above, the best predictors for postmenopausal osteoporosis in Shanghai Chinese postmenopausal women were osteocalcin (OC) and procollagen type 1 N-terminal propeptide (P1NP) [the areas under the ROC curve (AUC)=0.746 and 0.761, respectively].Conclusion: Serum periostin may not be used as a marker of systemic bone metabolism in Shanghai Chinese postmenopausal women without prior fracture. In addition, serum P1NP and OC levels may be the predictors of osteoporosis occurrence in Chinese postmenopausal women.Keywords: postmenopausal women, periostin, bone turnover markers, bone mineral density

Context Zoledronate is used to prevent bone loss following denosumab discontinuation but its efficacy differs among studies. Objective To test if the duration of denosumab treatment affects the efficacy of subsequent zoledronate infusion. Methods This multicenter, prospective cohort study, conducted at 2 Greek and 1 Dutch bone centers, included 47 postmenopausal women (n = 47) who received a single zoledronate infusion 6 months after the last denosumab injection and then were followed for 1 year. Twenty-seven women received ≤ 6 denosumab injections (≤ 6 Group) and 20 received > 6 denosumab injections (> 6 Group). The main outcome measure was changes in lumbar spine (LS) bone mineral density (BMD). Results At 12 months LS-BMD values were maintained in the ≤ 6 Group (0.98 ± 0.10 to 0.99 ± 0.9 g/cm2, P = 0.409) but decreased significantly in the > 6 Group (1.0 ± 0.11 to 0.93 ± 0.12 g/cm2, P 6 Group (−7.0%). In the whole cohort, the duration of denosumab treatment was negatively correlated with the percentage change of LS-BMD (rs = −0.669, P Conclusion The duration of denosumab treatment significantly affects the efficacy of subsequent zoledronate infusion to maintain BMD gains. Frequent follow-up of patients treated with denosumab longer than 3 years is advisable as additional therapeutic interventions may be needed.

RATIONALE & OBJECTIVE: Bone biopsy remains the gold standard for diagnosing renal osteodystrophy as comparable noninvasive alternatives have yet to be established. This study investigated the diagnostic accuracy of biochemical markers of skeletal remodeling to predict bone turnover. STUDY DESIGN: Cross-sectional retrospective diagnostic test study. SETTING & PARTICIPANTS: Patients with chronic kidney disease glomerular filtration rate categories 4-5, including patients treated with dialysis (G4-G5D) and kidney transplant recipients with successful transiliac bone biopsies. TESTS COMPARED: Bone turnover as determined by bone histomorphometry was compared with the following biochemical markers: full-length (amino acids 1-84) "biointact" parathyroid hormone (PTH), bone-specific alkaline phosphatase (BsAP), intact procollagen type I N-terminal propeptide (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b). OUTCOME: Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC), sensitivity, specificity, and negative and positive predictive values. Optimal diagnostic cutoffs were determined in an exploration cohort (n = 100) and validated in a separate cohort (n = 99). RESULTS: All biomarkers differed across categories of low 33 (17%), normal 109 (55%), and high 57 (29%) bone turnover. AUC values were in the range of 0.75-0.85. High negative predictive values (≥90%) were found for both high and low bone turnover, indicating the ability to rule out both conditions using the suggested biomarker cutoffs. The highest diagnostic performances were seen with combinations of biomarkers, with overall diagnostic accuracies of 90% for high turnover, and 78% for low turnover. Results were comparable for kidney transplant candidates and recipients in a sensitivity analysis. LIMITATIONS: The single-center approach and heterogeneity of the study cohort are main limitations of this study. CONCLUSIONS: We conclude that the diagnostic performance of biochemical markers of bone turnover is acceptable, with clinical utility in ruling out both high and low turnover bone disease. ispartof: AMERICAN JOURNAL OF KIDNEY DISEASES vol:79 issue:5 pages:667-+ ispartof: location:United States status: published

The direct effect of TSH on bone metabolism in vivo is difficult to capture as the changes of its concentrations are followed by respective alterations of thyroid hormone levels. We evaluated the effect of recombinant human TSH (rhTSH) on sclerostin and other bone markers in 29 patients after total thyroidectomy for differentiated thyroid cancer (DTC), without any signs of disease recurrence, who received L-thyroxine, most at non-suppressive doses. For two consecutive days, the patients were administered a standard dose of 0.9 mg rhTSH, i.m. Concentrations of sclerostin, osteocalcin, β-CrossLaps, PTH, and some other parameters, were measured before and five days after the first rhTSH administration. The greater the increase in TSH concentration (∆TSH), the greater the decrease in: ∆sclerostin (r = −0.672, p &lt, 0.001), ∆β-CrossLaps (r = −0.580, 0.001) and ∆osteocalcin (r = −0.405, p = 0.029) levels, were recorded. The degree of TSH increase depended on the baseline PTH (r = 0.651, 0.001), age, and creatinine concentrations. rhTSH strongly inhibited bone turnover, thus, TSH—independently of thyroid hormones—exerted a direct protective effect on bone metabolism. Baseline PTH affected the magnitude of TSH increase and the degree of lowering in sclerostin and β-CrossLaps that suggest factors affecting PTH may play a role in the effect of TSH on the bone.

Background Previous research conducted among institutionalized older adults has reported increased bone turnover markers (BTMs) in those subjects with mobility limitation. However, the association between walking speed and bone metabolism has not been well described in community-dwelling older adults. Methods The National Health and Nutrition Examination Survey 1999-2000 and 2001-2002 cycles were used to determine the association between the 20-feet walking speed test and bone alkaline phosphatase (BAP) and the cross-linked N-telopeptides of type I bone collagen (NTx). Sex-specific general linear models adjusted for potential confounders were assembled to examine the independent association between the time to complete the walking speed test grouped into quartiles and the logarithmic transformations of BAP and NTx levels. Results Of 2,521 older adults, 25.8% were defined as having mobility limitation. In both genders, BTM levels progressively increased as the time to complete the walking test also increase. Indeed, women and men who completed the walking speed test in the worst time quartile had on average 6% and 2.8% higher NTx levels than their counterparts who completed the test in the best time quartile, respectively. Likewise, BAP levels also progressively increased across walking speed time quartiles, but to a lesser degree. Notably, NTx levels were 4.7% and 2.6% higher in women and men with mobility limitation than those without, respectively. In contrast, BAP levels did not significantly differ in older adults regardless of their mobility limitation status. Conclusions Community-dwelling older adults with slower walking speeds and mobility limitation consistently had evidence of increased bone resorption. Thus, the present findings indicate that older adults with mobility limitation should be considered at risk of osteoporosis.

Background and Objectives: The aim of this study was to determine the influence of bone turnover markers, namely the N-terminal cross-linking telopeptide (NTx) and alpha C-terminal cross-linking telopeptide of type I collagen (α-CTx), in detecting bone metastasis (bone-only) in breast cancer (BC) patients, as well as to determine whether this effect is related to changes in bone mineral density (BMD). Materials and Methods: The participants in this study comprised 30 postmenopausal BC patients with bone metastases (age range: 59.56 ± 9.02), 20 postmenopausal BC patients without bone metastases (age range: 55.30 ± 11.55), and 20 healthy postmenopausal female controls (age range: 55.55 ± 5.85). Bone turnover markers (serum NTx and urine α-CTx) were measured using the ELISA method. A densitometer using dual-energy X-ray absorptiometry (DEXA) was used to analyze the BMD, and tumor markers were measured using the chemiluminescent immunometric assay. Results: The corresponding levels of serum NTx (p = 0.004), parathyroid hormone (PTH) (p = 0.001), and urine α-CTx (p &lt, 0.001) of BC patients were found to be higher than the standard levels. After the BC patients were divided into subgroups on the basis of the presence of metastasis, the urine α-CTx levels (p = 0.001) were seen to be at critically high levels in those patients suffering from BC with metastasis. Though the BMD values in the lumbar spine (p &lt, 0.001) and femoral neck (p = 0.001) were found to be significantly low in BC patients, no statistically substantial difference in the BMD levels of BC patients suffering from metastasis was observed. It was observed that urine α-CTx (specificity: 70%, sensitivity: 85%) values are critical factors that differentiate BC patients with metastasis from BC patients without metastasis. Conclusions: We found that alterations in bone turnover could be detected by using the values of urine α-CTx while differentiating BC patients with metastasis from BC patients without metastasis. Using the biochemical markers of bone turnover and BMD together would be pertinent for determining the level of metastasis present and examining the efficiency of bone density preservation therapy. Ideally, BMD measurement would be evaluated together with biochemical markers.

BackgroundOsteoporosis is a common complication of acute fracture, which can lead to fracture delayed union or other complications and resulting in poor fracture healing. Bisphosphate is a common anti-osteoporosis drug, but its application in fracture patients is still controversial because of its inhibitory effect on bone resorption.MethodStudies were acquired from literature databases in accordance with established inclusion criteria. Standard mean difference (SMD) and 95% confidence intervals (Cls) were calculated to evaluate the effectiveness of the bisphosphonates treatment in fracture patients. Data analysis was conducted with the Review Manager 5.4.1 software.ResultsA total of 16 studies involving 5022 patients obtained from selected databases were examined. As expected, bisphosphate had no significant effect on fracture healing time, but it could significantly increase BMD and prevent osteoporosis. Meanwhile, bisphosphate can inhibit both bone resorption and bone formation markers, resulting in low bone turnover state.ConclusionThis meta-analysis showed that bisphosphonate have no significant effect on fracture healing time but they do increase the changes in BMD and reduce bone synthesis and resorption markers. Early application of bisphosphonates after injury in the appropriate patient population should be considered.

Renal osteodystrophy (ROD) represents bone disorders related to chronic kidney disease (CKD) and several bone biomarkers are used clinically to predict ROD in CKD and hemodialysis (HD) patients. Serum albumin associates with inflammation other than nutritional status in these patients. Chronic inflammation is proved to relate with bone loss, however, the influence of hypoalbuminemia on bone biomarkers is still unclear. In this study, we evaluated the pattern of bone biomarker changes and further studied the influence of hypoalbuminemia on these biomarkers. A total of 300 maintenance HD patients were evaluated and 223 HD patients were included in the study. The patients were grouped according to serum parathyroid hormone (PTH) levels (PTH ≤150 pg/mL, PTH 150-300 pg/mL, PTH 300-600 pg/mL and PTH >600 pg/mL). Bone biomarkers and inflammatory markers were measured and their relation with PTH levels was determined. Significantly increased interleukin-6 (IL-6) and lower albumin levels were noted among PTH>600 pg/mL group. Bone turnover markers were significantly higher in PTH >600 pg/mL group (p< 0.05). Hypoalbuminemia significantly increased the fibroblast growth factor-23 (FGF-23) and procollagen type 1N-terminal propeptide (P1NP) in PTH ≤150 pg/mL, PTH 150-300 pg/mL, PTH 300-600 pg/mL groups, whereas no such relation was noted among PTH> 600 ng/dL group. In conclusion, hypoalbuminemia represents a chronic inflammation which differently relates to bone turnover markers according to serum PTH levels in SHPT patients. Thus, serum albumin measurement should be considered in determining bone disorders among these patients.

BACKGROUND: Bone quality and other preoperative predictive factors may affect implant migration and the survival of knee arthroplasty.METHODS: In a prospective cohort of 100 consecutive patients (65 women) at a mean age of 67.7 years (range 39-87 years), we investigated preoperative predictors of postoperative tibial component migration in cemented and cementless total knee arthroplasties or cemented unicompartmental knee arthroplasty. Predictors consisted of Knee Injury and Osteoarthritis Outcome Score (KOOS) and Oxford Knee Score, questionnaires, bone turnover markers of CTX and P1NP, systemic bone mineral density (BMD), and knee osteoarthritis (OA) grade. Tibial component migration was measured with radiostereometry postoperative, at 1 and 2 years of follow-up.RESULTS: Between 1 and 2 years, 19 tibial components migrated continuously (maximum total point motion [MTPM] > 0.2 mm). In general, there was no difference in age, body mass index, BMD, KOOSs, or OA grade between patients with continuous tibial migration compared to patients without continuous migration (P > .11). However, cementless tibial components with continuous migration had a lower KOOS pain score (more pain), lower vitamin D, and a higher bone turnover (CTX) value than patients without continuous migration. There was no association between the BMD and MTPM at 1-year follow-up regardless of prothesis type (P > .17). Patients with osteoporosis and normal BMD had similar mean tibial component MTPM at 2 years (3 prostheses combined; P = .34).CONCLUSION: Migration of tibial components inserted with or without bone cement was not affected by the preoperative bone quality in terms of systemic BMD, bone turnover markers, and OA grade in the knee.

To assess the time from fracture until bone turnover markers (BTM), which are biochemical markers reflecting in vivo bone formation and resorptive activity, have returned to a stable level since BTM have been shown to be at least as good as bone mineral density in monitoring the effect of anti-resorptive treatment in osteoporosis. This study searched for articles in PUBMED, CINAHL, Medline, EM-BASE, and Cochrane, and identified 3486 unique articles. These articles were screened based on predefined inclusion and exclusion criteria. Seven articles addressing time to normalization of either CTX, PINP, osteocalcin, or bone-specific alkaline phosphatase after a recent fracture were identified and these were analyzed qualitatively. CTX appeared to return to baseline within 6 months. PINP appeared to return to baseline within 6 months and interestingly dip below baseline after a year. Osteocalcin was elevated throughout the first year after a fracture, with most changes in the first 6 months. Bone-specific alkaline phosphatase (BAP) was increased for up to a year, however with a discrepancy between used assays. Seven studies were identified, showing CTX and PINP to return to baseline within 6 months. OC was elevated for 12 months. BAP was increased for up to a year. However, none of these studies had fasting patients and a long follow-up period with regular measurements. The studies could indicate that the BTM CTX and PINP have returned to baseline within 6 months; however, further studies are needed assessing pre-analytical factors while having a long follow-up. Bone turnover markers appear as good as or better than bone mineral density in monitoring the effect of anti-resorptive medication in osteoporosis. This study tries to identify the time from fracture until BTM are back at baseline. Most studies did not however take pre-analytical variation into consideration. Further research is therefore needed.

The relationships of osteocalcin (OC) and C-telopeptide of type I collagen (CTX) with long-term incidence of hip fracture were examined in 1680 post-menopausal women from a population-based study. CTX, but not OC, levels were associated with incident hip fracture in these participants, a relationship characterized by an inverted U-shape.IntroductionWe sought to investigate the relationships of OC, a marker of bone formation, and CTX, a marker of bone resorption, with long-term incidence of hip fracture in older women.MethodsWe included 1680 women from the population-based Cardiovascular Health Study (mean [SD] age 74.5 [5.0] years). The longitudinal association of both markers with incidence of hip fracture was examined using multivariable Cox models.ResultsDuring a median follow-up of 12.3years, 288 incident hip fractures occurred. Linear spline analysis did not demonstrate an association between OC levels and incident hip fracture. By contrast, increasing levels of CTX up to the middle-upper range were associated with a significantly greater risk of hip fracture (HR = 1.52 per SD increment, 95% CI = 1.10-2.09), while further increases were associated with a marginally non-significant lower risk (HR = 0.80 per SD increment, 95% CI = 0.63-1.01), after full adjustment for potential confounders. In analyses of quartiles, CTX exhibited a similar inverted U-shaped relationship with incident fracture after adjustment, with a significant association observed only for the comparison of quartile 3 to quartile 1 (HR = 1.63, 95% CI = 1.10-2.43). In a subset with available measures, both OC and CTX were inversely associated with bone mineral density of the hip.ConclusionCTX, but not OC, levels were associated with incident hip fracture in post-menopausal women, a relationship characterized by an inverted U-shape. These findings highlight the complex relationship of bone turnover markers with hip fracture risk.

Background Biochemical bone turnover markers (BTM) are useful tools to assess bone remodeling at the cellular level. N-terminal propeptide of type I procollagen (PINP) has been recommended as a reference marker for bone formation in research studies. Methods We describe the results of a multicenter study for routine clinical laboratory assays for PINP in serum and plasma. Four centers (Athens, Greece [GR], Copenhagen, Denmark [DK], Liege, Belgium [BE] and Sheffield, United Kingdom [UK]) collected serum and plasma (EDTA) samples from 796 patients presenting to osteoporosis clinics. Specimens were analyzed in duplicate with each of the available routine clinical laboratory methods according to the manufacturers’ instructions. Passing-Bablok regressions, Bland-Altman plots, V-shape evaluation method and the concordance correlation coefficient for PINP values between serum and plasma specimens and between methods were used to determine the agreement between results. A generalized linear model was employed to identify possible variables that affected the relationship between the methods. Results We showed that both EDTA plasma and serum were suitable for PINP determination. We observed a significant proportional bias between Orion radioimmunoassay and the automated methods for PINP (Roche Cobas and IDS iSYS), which both gave very similar results. The multivariate model did not improve the excellent correlation that was observed between the methods. Conclusions Harmonization of PINP assays is possible by applying a correction factor or correctly assigning the values of the calibrators. This work will benefit from further collaboration between assays manufacturers and clinical laboratory professionals.

The aim of the study was to investigate the association of Cystatin C (CysC) to biochemical markers of bone turnover and bone mass, and to evaluate its prognostic significance in elderly males with chronic heart failure (CHF).A prospective cohort study was executed on sixtyeight males (mean age 68±7 years) with mild to moderate CHF, together with 19 of corresponding age- and body mass index-matched healthy individuals who underwent cardio vascular, bone mineral density (BMD), and body com position assessment. Biochemical assessment of all subjects included NT-pro-BNP, parathyroid hormone (PTH), 25-hydroxy vitamin D (25(OH)D), CysC, and biochemical markers of bone turnover including osteocalcin (OC), alkaline phosphatase (ALP), β-CrossLaps (β-CTx), osteoprotegerin (OPG), and receptor activator of nuclear factor κB ligand (RANKL).Serum CysC was significantly increased in males with CHF in comparison to healthy control ones. A significant positive association was found between CysC levels and OC in males with CHF, while OC and β-CTx increased in increasing CysC tertiles. In multivariate regression analysis, OC and smoking were a significant determinant of CysC in males with CHF. Level of CysC was found to be positively associated with an increased fatal risk in males with CHF.Serum osteocalcin is an independent predictor of CysC level in elderly males with CHF. Higher CysC level showed a negative relation to survival and bone loss in males with CHF. Further research is needed to confirm the potential role of CysC in the crosstalk between heart, kidney, bone, and energy metabolism in CHF.Cilj studije je bio da se ispita povezanost cistatina C (CisC) i biohemijskih markera metabolizma kosti i mineralne koštane gustine, kao i da se proceni prognostički značaj CisC kod starijih muškaraca sa hroničnom srčanom insuficijencijom (HSI).Ovo istraživanje je prospektivna studija kohorte koju je činilo šezdeset osam muškaraca (prosečne starosti 68±7 godina života) sa blagom do umerenom HSI i 19 zdravih osoba odgovarajuće starosti i indeksa telesne mase. Svi ispitanici su podvrgnuti proceni kardiovaskularnog sistema, mineralne koštane gustine i telesnog sastava. Biohemijska merenja kod svih ispitanika su uključivala određivanje NT-pro-BNP, paratiroidnog hormona (PTH), 25-hidroksi vitamina D (25 (OH) D), CisC i biohemijskih markera metabolizma kosti, uključujući osteokalcin (OC), alkalnu fosfatazu (ALP), beta-CrossLaps (b-CTx), osteoprotegerin (OPG) i ligand za receptor aktivator nuklearnog faktora B (RANKL).Serumski CisC je značajno povećan u muškaraca sa HSI u poređenju sa nivoom kod zdravih osoba. Značajna pozitivna povezanost detektovana je između nivoa CisC i OC kod muškaraca sa HSI, i vrednosti OC i b-CTx su povećane kod pacijenata u rastućim CisC tercijarima. U multivarijantnoj regresionoj analizi je pokazano da su OC i pušenje znač ajne determinante nivoa CisC kod muškaraca sa HSI. Nivo CisC je u pozitivnoj korelaciji sa povećanim rizikom za mortalitet kod muškaraca sa HSI.Serumski osteokalcin je nezavisan prediktor nivoa CisC kod starijih muškaraca sa HSI. Povećan nivo CisC je pokazao negativnu povezanost sa preživljanjem i gubitkom kosti kod muškaraca sa HSI. Potrebno je da buduća istraživanja potvrde potencijalnu ulogu CisC u komunikaciji između srca, bubrega, kosti i energetskog metabolizma u hroničnoj srčanoj insuficijenciji.

Purpose: To examine efficacy of 12 months Football Fitness offered twice per week on bone mineral density (BMD), bone turnover markers (BTM), postural balance, muscle strength and body composition in women treated for early-stage breast cancer (BC).Methods: Women treated for early-stage BC were randomised to Football Fitness (FFG, n=46) or control (CON, n=22) in a 2:1 ratio for 12 months, with assessments performed at baseline, 6 months and 12 months. Outcomes were total body-, lumbar spine- and proximal femur BMD, total body lean and fat mass, leg muscle strength, postural balance, and plasma amino-terminal propeptide of type 1 procollagen (P1NP), osteocalcin and C-terminal telopeptide of type 1 collagen (CTX). Intention-to-treat (ITT) analyses and per-protocol analyses (≥50% attendance in FFG) were performed using linear mixed models.Results: Participants in FFG completing the 12-month intervention (n=33) attended 0.8 (SD=0.4) sessions per week. Intention to treat analysis of mean changes over 12 months showed significant differences in L1-L4 BMD (0.029 g/cm2 , 95%CI: 0.001 to 0.057), leg press strength (7.2 kg, 95%CI: 0.1 to 14.3) and postural balance (-4.3 n need of support, 95%CI: -8.0 to -0.7) favouring FFG compared to CON. In the per-protocol analyses, L1-L4 and trochanter major BMD were improved (p=0.012 and 0.030, respectively) in FFG compared to CON. No differences were observed between groups in BTMs in the ITT or per protocol analyses.Conclusion: One year of Football Fitness training may improve L1-L4 BMD, leg muscle strength and postural balance in women treated for early-stage breast cancer.

Funding Information: Funding: This research was funded by Vitaflo International as part of Ph.D. grant. Funding Information: Conflicts of Interest: A.D. research funding from Vitaflo International, financial support from Nutri-cia, Mevalia & Vitaflo International to attend study days & conferences. S.E. research funding from Nutricia, financial support from Nutricia & Vitaflo International to attend study days & conferences. A.P. has received an educational grant from Cambrooke Therapeutics and grants from Vitaflo International, Nutricia, Merck Serono, Biomarin and Mevalia to attend scientific meetings. C.A. received honoraria from Nutricia and Vitaflo International to attend study days and conferences. J.C.R. member of the European Nutritionist Expert Panel (Biomarin), the Advisory Board for Applied Pharma Research and Nutricia, and received honoraria as a speaker from APR, Merck Serono, Biomarin, Nutricia, Vitaflo, Cambrooke, PIAM and Lifediet. A.M. research funding & honoraria from Nutricia, Vitaflo International & Merck Serono, Member of European Nutrition Expert Panel (Merck Serono international), member of Sapropterin Advisory Board (Merck Serono international), member of the Advisory Board Element (Danone-Nutricia). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm. Aims: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein glycomacropeptide substitutes (CGMP-AA) as their main protein source. Methodology: A total of 48 subjects completed the study, 19 subjects in the L-AA group (median age 11.1, range 5–6 years) and 29 subjects in the CGMP-AA group (median age 8.3, range 5–16years). The CGMP-AA was further divided into two groups, CGMP100 (median age 9.2, range 5–16years) (n = 13), children taking CGMP-AA only and CGMP50 (median age 7.3, range 5–15years) (n = 16), children taking a combination of CGMP-AA and L-AA. Dual X-ray absorptiometry (DXA) was measured at enrolment and 36 months, peripheral quantitative computer tomography (pQCT) at 36 months only, and serum blood and urine bone turnover markers (BTM) and blood bone biochemistry at enrolment, 6, 12, and 36 months. Results: No statistically significant differences were found between the three groups for DXA outcome parameters, i.e., BMDa (L2–L4 BMDa g/cm2 ), bone mineral apparent density (L2–L4 BMAD g/cm3 ) and total body less head BMDa (TBLH g/cm2 ). All blood biochemistry markers were within the reference ranges, and BTM showed active bone turnover with a trend for BTM to decrease with increasing age. Conclusions: Bone density was clinically normal, although the median z scores were below the population mean. BTM showed active bone turnover and blood biochemistry was within the reference ranges. There appeared to be no advantage to bone density, mass, or geometry from taking a macropeptide-based protein substitute as compared with L-AAs. publishersversion published

The aim of this study was to evaluate the effect of anti-tumor necrosis factor α (anti-TNF-α) therapy in combination with methotrexate on bone remodeling and osteoclastogenesis in female patients with RA. Serum levels of bone turnover markers (i.e., C- and N-terminal propeptides of type I procollagen (PICP and PINP), C- and N-terminal cross-linking telopeptides of type I collagen (CTX-I and NTX-I), and soluble receptor activator of nuclear factor κB ligand (sRANKL) and osteoprotegerin (OPG)) were determined by immunoassay at baseline and 15 months after initiation of treatment. Bone mineral density was measured by dual-energy x-ray absorptiometry. We found a significant decrease in serum PINP levels, a biomarker of bone formation, and higher levels of CTX-I and sRANKL indicative of increased bone resorption in RA patients prior to TNFαI treatment compared to the controls. Anti-TNF-α therapy was effective in improving bone metabolism in RA patients as reflected in a decrease in CTX-I (at least partially due to the RANKL/OPG reduction) and a concomitant increase in PINP levels. The bone metabolism changes were independent of the type of TNFαI used. PINP and CTX-I were found to be useful markers of bone metabolism, which may prove the effectiveness of TNF-α therapy earlier than the bone density assessment.

Purpose Bone turnover markers (BTM) are gaining ground in clinical practice but to fully use their potential there is a need for establishing valid reference intervals (RI). Consequently, the purpose of the study was to establish general RI as well as suggested clinical RI for carboxy-terminal cross-linked telopeptide of type I collagen (β-CTX), pro-collagen type I N-terminal propeptide (PINP), osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP) in children and adolescents. Method BTM were measured on Danish children and adolescents participating in the CHAMPS-study DK. A total of 762 participants were included (8–18 years, 50.4% girls) contributing a total of 1410 study visits. The RI was calculated based on 2-years age spans. Participants with biochemical signs of metabolic bone disease were excluded. Results The differences in RI between age groups clearly reflect changes in growth with an initial increase in BTM, greatest in boys, and a subsequent decrease most pronounced in girls. β-CTX and PINP are markers most affected by these changes, compared to OC and bone ALP. The suggested clinical 95% RI included participants with vitamin D insufficiency but no biochemical signs of metabolic bone disease which did not markedly alter the RI. Conclusion RI for β-CTX, PINP, OC and bone ALP varies with age and sex. β-CTX and PINP which reflect bone resorption and formation processes are mostly affected by these changes. We suggest a set of clinically applicable 95% RI for the four BTM to heighten the usefulness and generalizability of the RI.

Background The Insulin‐like growth factor‐1 (IGF‐1) is primarily synthesized by hepatocytes in a growth hormone (GH)‐dependent manner, it is also produced by bone and muscle. The effects of exercise on the associations between IGF‐1 levels and bone turnover markers (BTM) were found in the previous studies. However, the associations between the levels of IGF‐1 and BTM, liver function tests, and skeletal muscle markers in adults with general physical activity were not clear. Methods Ninety‐four participants were recruited from healthy survey. Blood samples were collected to analyze the levels of IGF‐1, total protein (TP), albumin (Alb), total bilirubin (T‐Bil), direct bilirubin (D‐Bil), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), lactate dehydrogenase (LDH), creatine kinase (CK), creatinine (CRTN), and glucose. Urine samples were collected to analyze the CRTN and deoxypyridinoline (Dpd) levels. Results The positively significant associations were found between the IGF‐1 levels and the levels of ALP, BALP, and CK, respectively. No significant associations were found between the IGF‐1 levels and the levels of TP, Alb, A/G, T‐Bil, D‐Bil, AST, ALT, LDH, glucose, urinary CRTN, urinary Dpd, and Dpd/CRTN ratios, respectively. Conclusion The serum IGF‐1 levels associated with the levels of skeletal muscle and bone formation markers (BFM), not the bone resorption markers under general physical activity in the healthy adults. The physician needs to consider the effects of bone formation and skeletal muscle markers on the IGF‐1 levels in the management of IGF‐1‐related disorders., In the healthy adults with general physical activity, the associations of the biomarkers of skeletal muscles, liver function and bone modulation with the circulating IGF‐1 levels were found: (1) The positively significant associations were found between the IGF‐1 levels and the levels of ALP, BALP and CK, respectively. (2) No significant associations were found between the IGF‐1 levels and the levels of AST, ALT, urinary CRTN, urinary Dpd, and Dpd/CRTN ratios respectively. (3) In conclusion, the serum IGF‐1 levels associated with the levels of skeletal muscle and bone formation markers, not the markers of bone resorption and liver function.

Weight loss is a major focus of research and public health efforts. Time-restricted eating (TRE) is shown to be effective for weight loss, but the impact on bone is unclear. Short-term TRE studies show no effect on bone mineral density (BMD), but no study has measured bone turnover markers. This secondary analysis examined the effect of 12 weeks of TRE vs. unrestricted eating on bone turnover and BMD. Overweight and obese adults aged 18–65 y (n = 20) were randomized to TRE (ad libitum 8-h eating window) or non-TRE. Serum N-terminal propeptide of type I collagen (P1NP), cross-linked N-telopeptide of type I collagen (NTX), and parathyroid hormone (PTH) levels were measured and dual-energy X-ray absorptiometry (DXA) scans were taken pre- and post-intervention. In both groups, P1NP decreased significantly (p = 0.04) but trended to a greater decrease in the non-TRE group (p = 0.07). The treatment time interaction for bone mineral content (BMC) was significant (p = 0.02), such that BMC increased in the TRE group and decreased in the non-TRE group. Change in P1NP was inversely correlated with change in weight (p = 0.04) overall, but not within each group. These findings suggest that TRE does not adversely affect bone over a moderate timeframe. Further research should examine the long-term effects of TRE on bone.

Optimisation of skeletal mineralisation in childhood is important to reduce childhood fracture and the long-term risk of osteoporosis and fracture in later life. One approach to achieving this is antenatal vitamin D supplementation. The Maternal Vitamin D Osteoporosis Study is a randomised placebo-controlled trial, the aim of which was to assess the effect of antenatal vitamin D supplementation (1000 IU/day cholecalciferol) on offspring bone mass at birth. The study has since extended the follow up into childhood and diversified to assess demographic, lifestyle and genetic factors that determine the biochemical response to antenatal vitamin D supplementation, and to understand the mechanisms underpinning the effects of vitamin D supplementation on offspring bone development, including epigenetics. The demonstration of positive effects of maternal pregnancy vitamin D supplementation on offspring bone development and the delineation of underlying biological mechanisms inform clinical care and future public-health policies.

Background Osteoporosis (OP) and osteoarthritis (OA) commonly coexist in postmenopausal females. The decrease in bone density and increase in bone resorption in postmenopausal females with OP may consequently affect the surgical outcome of total knee arthroplasty (TKA). However, clinicians often ignore monitoring the treatment of OP in the perioperative management of TKA. Bone turnover marker (BTM) can timely and accurately reflect bone metabolism to monitor the treatment of OP. The purpose of this study was to investigate the effect of BTM monitoring to guide the treatment of OP in postmenopausal females undergoing TKA. Methods Postmenopausal females with OP who underwent primary unilateral TKA were randomly divided into two groups (monitoring group and control group), given oral medication (alendronate, calcitriol, and calcium), and followed for 1 year. In the monitoring group, serum BTMs (C-telopeptide of type I collagen (CTX-I), N-terminal propeptide of type I procollagen (PINP), and 25(OH)D) were assessed preoperatively and repeated postoperatively; alendronate was withdrawn when CTX-I and PINP reached the reference interval; and calcitriol and calcium were withdrawn when 25(OH)D reached the reference interval. In the control group, oral medication was implemented for a uniform duration of 3 months. During the 1-year follow-up, the mean maximum total point motion (MTPM) of the tibial component, bone mineral density (BMD), visual analog scale (VAS) score, range of motion, and Oxford Knee Score (OKS) score were obtained. Results In the monitoring group, BTM monitoring prolonged the medication duration, but did not cause more adverse reactions than in the control group. The mean MTPM values at 6 m and 12 m in the monitoring group were lower than those in the control group, and the BMD at 12 m in the monitoring group was significantly higher than that in the control group. Patients in the monitoring group had lower VAS scores at 6 m and higher OKS scores at 6 m and 12 m than those in the control group. Conclusion In postmenopausal females with osteoporosis undergoing primary TKA, the application of BTM monitoring to guide the treatment of osteoporosis can enhance bone density, maintain prosthesis stability, and improve surgical outcome. Trial registration ChiCTR ChiCTR-INR-17010495. Registered on 22 January 2017

Young Indian women may be at risk of poor bone health due to malnutrition. The aim of this study was to examine the effects on bone metabolism of a nutritional supplement in women aged 25 to 44. The nutritional supplement was a protein-rich beverage powder fortified with multi-micronutrients including calcium (600 mg), vitamin D (400 IU), and vitamin K (55 mcg) per daily serving, while a placebo supplement was low-protein non-fortified isocaloric beverage powder. This 6-month randomised, controlled trial showed favorable changes in bone turnover markers (decreased) and calcium homeostasis, such changes in older adults have been associated with slowing of bone loss and reduced fracture risk. For example, serum CTX decreased by about 30% and PINP by about 20% as a result of the increase in calcium intake. There were also changes in the ratio of carboxylated to undercarboxylated osteocalcin and such changes have been linked to a slowing of bone loss in older subjects. For example, the ratio increased by about 60% after 3 months as a result in the improvement in vitamin K status. Finally, there were improvements in the status of B vitamins, and such changes have been associated with reductions in homocysteine, but it is uncertain whether this would affect fracture risk. The product was generally well tolerated. This study shows the nutritional supplement holds promise for improved bone health among young Indian women.

Background: Hyperbaric oxygen therapy (HBOT) is useful in the treatment of complications due to radiotherapy in patients with neoplasm. Its effects on bone metabolism are unclear. In our study, we analyzed the effects of HBOT on bone remodeling in oncological patients with radiotherapy. Materials and methods: Prospective clinical study in 23 patients with neoplasms undergoing treatment with HBOT due to complications of radiotherapy (hemorrhagic cystitis, proctitis or radionecrosis) and 25 patients with chronic anal fissure. The average number of HBOT sessions was 20 ± 5 (100% oxygen, 2.3 atmospheres and 90 min per day). Serum levels of aminoterminal propeptide of type I collagen (P1NP), C terminal telopeptide of type I collagen (CTX), alkaline phosphatase (AP), 25hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), were measured at 3 time points: T0 (before beginning HBOT), T1 (at the end of HBOT) and T2 (6 months after HBOT). Results: At baseline, the patients with neoplasm have higher bone turnover than those with anal fissure. These differences were 41% in CTX (0.238 ± 0.202 ng/mL in neoplasm and 0.141 ± 0.116 ng/mL in fissure; p = 0.04), 30% for PTH (46 ± 36 pg/mL in neoplasm and 32 ± 17 pg/mL in fissure; p = 0.04) and 15% for alkaline phosphatase (80 ± 24 U/L in neoplasm and 68 ± 16 U/L in fissure; p = 0.04). In the group with neoplasm, the values of P1NP decreased 6% after HBOT (T0: 49 ± 31 ng/mL, T2: 46 ± 12 ng/mL; p = 0.03). Also, there were non-significant decreases in PTH (–34%) and CTX (–30%). Conclusions: Patients with neoplasm and complications with radiotherapy have an increase in bone remodeling that may be diminished after HBOT.

The relationship between endocrine hormones and the spectrum of rheumatic conditions has long been discussed in the literature, focusing primarily on sexual hormones, such as estrogens, androgens, prolactin (PRL). Estrogens are indeed involved in the pathogenesis of the main inflammatory arthritis thanks to their effects on the immune system, both stimulatory and inhibitory. The PRL system has been discovered in synovial tissue of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), patients and has been propose as a new potential therapeutic target. Besides sexual hormones, in the last years scientific interest about the crosstalk of immune system with other class of hormones has grown. Hormones acting on the bone tissue (i.e. parathyroid hormone, vitamin D) and modulators of the Wnt pathway (i.e. Dickkopf-1) have been demonstrated to play active role in inflammatory arthritis course, defining a new field of research named osteoimmunology. PTH, which is one of the main determinants of Dkkopf-1, plays a crucial role in bone erosions in RA and a correlation between PTH, Trabecular Bone Score (TBS) and disease activity has been found in ankylosing spondylitis (AS). In PSA is under studying the interaction among IL-17 and bone metabolism. The purpose of this review is to discuss and summarize the recent data about the interaction between endocrine hormone and immune system in the main rheumatic disorders, covering in particular the role of bone-related hormones and cytokines. We will describe this relationship from a biochemical, diagnostic and therapeutic perspective, with a particular focus on RA, PsA and AS.

Context Denosumab discontinuation is characterized by an increase in bone turnover overriding pretreatment status, a rapid bone loss in the majority and multiple vertebral fractures (VFx) in some patients. Methods A working group of the European Calcified Tissue Society performed an updated systematic review of existing literature on changes of bone turnover, bone mineral density (BMD), and fracture risk after denosumab discontinuation and provided advice on management based on expert opinion. Results Important risk factors for multiple VFx following denosumab cessation are prevalent VFx, longer duration off therapy, greater gain in hip BMD during therapy, and greater loss of hip BMD after therapy according to a retrospective analysis of the FREEDOM Extension Study. Case series indicate that prior bisphosphonate therapy mitigates the biochemical rebound phenomenon after denosumab discontinuation, but it is uncertain whether this attenuation prevents BMD loss and fractures. Current evidence indicates partial efficacy of subsequent antiresorptive treatment with results seemingly dependent on duration of denosumab treatment. Conclusions A careful assessment of indications to start denosumab treatment is advised, especially for younger patients. A case for long-term treatment with denosumab can be made for patients at high fracture risk already on denosumab treatment given the favorable efficacy and safety profile. In case of denosumab discontinuation, alternative antiresorptive treatment should be initiated 6 months after the final denosumab injection. Assessment of bone turnover markers may help define the optimal regimen, pending results of ongoing randomized controlled trials. Patients who have sustained VFx should be offered prompt treatment to reduce high bone turnover.

Although diuretics are often prescribed to control fluid overload, they can change Chronic kidney disease-mineral and bone disorder (CKD-MBD) parameters. Previous studies have shown an association between diuretic prescription and changes in both calciuria and parathormone levels. However, the causal relationship could not be confirmed. In addition, the effects of diuretics on bone mineral density and turnover markers are yet to be established. To evaluate the effects of diuretics on CKD-MBD, we have performed a prospective randomized trial comparing hydrochlorothiazide with furosemide in a stage 3CKD population followed for 1 year. Furosemide increased bone remodeling and parathormone levels, whereas hydrochlorothiazide attenuated parathyroid hormone rise and decreased bone turnover markers., Highlights • Diuretics may change parathormone (PTH), although a randomized trial was missing. • Patients with CKD were randomized to either Furosemide or Hydrochlorothiazide. • Furosemide increased PTH levels, CTx and P1NP. • Hydrochlorothiazide attenuated PTH rise and decreased CTx and P1NP.

Background Glucocorticoid therapy is the most common cause of iatrogenic osteoporosis. Less is known regarding the effect of glucocorticoids when used as replacement therapy on bone remodelling in patients with adrenal insufficiency. Enhanced intracellular conversion of inactive cortisone to active cortisol, by 11 beta-hydroxysteroid dehydrogenase type 1(11β-HSD1) and other enzymes leading to alterations in glucocorticoid metabolism, may contribute to a deleterious effect on bone health in this patient group. Methods Study design: An open crossover prospective study randomizing ten hypopituitary men, with severe ACTH deficiency, to three commonly used hydrocortisone dose regimens. Measurements: Following 6 weeks of each regimen, patients underwent 24-h serum cortisol/cortisone sampling, measurement of bone turnover markers, and a 24-h urine collection for measurement of urinary steroid metabolites by gas chromatography-mass spectrometry (GC-MS). Serum cortisone and cortisol were analysed by liquid chromatography-mass spectrometry (LC-MS). Results Dose-related and circadian variations in serum cortisone were seen to parallel those for cortisol, indicating conversion of ingested hydrocortisone to cortisone. The median area under the curve (AUC) of serum cortisone was significantly higher in patients on dose A (20 mg/10 mg) [670.5 (IQR 621–809.2)] compared to those on dose C (10 mg/5 mg) [562.8 (IQR 520.1–619.6), p = 0.01]. A negative correlation was observed between serum cortisone and bone formation markers, OC [1–49] (r = − 0.42, p = 0.03), and PINP (r = − 0.49, p = 0.01). There was a negative correlation between the AUC of night-time serum cortisone levels with the bone formation marker, OC [1–49] (r = − 0.41, p = 0.03) but there were no significant correlations between day-time serum cortisone or cortisol with bone turnover markers. There was a negative correlation between total urinary cortisol metabolites and the bone formation markers, PINP (r = − 0.39, p = 0.04), and OC [1–49] (r = − 0.35, p = 0.06). Conclusion Serum cortisol and cortisone and total urinary corticosteroid metabolites are negatively associated with bone turnover markers in patients receiving replacement doses of hydrocortisone, with nocturnal glucocorticoid exposure having a potentially greater influence on bone turnover. Trial registration Irish Medicines Board Clinical Trial Number – CT900/459/1 and EudraCT Number – 2007-005018-37. Registration date: 07-09-2007.

Background Long-term treatment with corticosteroids causes loss of bone density, but the effects of using short-term high-dose systemic-corticosteroid therapy to treat acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to determine whether high-dose corticosteroid therapy affected bone turnover markers (BTMs) to a greater extent compared to low-dose corticosteroid therapy. Methods The CORTICO-COP trial (NCT02857842) showed that an eosinophil-guided corticosteroid intervention led to approximately 60% lower accumulated corticosteroid dose for hospitalized patients with AECOPD (low-dose group) compared with 5-day standard corticosteroid treatment (high-dose group). We compared the levels of BTMs C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) in 318 participants during AECOPD and at 1- and 3-month follow-up visits. Results CTX decreased and P1NP increased significantly over time in both treatment groups. There were no significant differences between the groups at 1- or 3-months follow-up for P1NP. A significant drop in CTX was seen at 3 months (down Δ24% from the baseline, p = 0.017) for the high dose group. Conclusion Short-term, high-dose systemic corticosteroid treatment caused a rapid suppression of biomarkers of bone resorption. Corticosteroids did not suppress biomarkers of bone formation, regardless of patients receiving low or high doses of corticosteroids. This therapy was, therefore, harmless in terms of bone safety, in our prospective series of COPD patients. Trial registration ClinicalTrials.gov Identifier: NCT02857842. Submitted August 2nd, 2016.

CONTEXT: Premenopausal women with idiopathic osteoporosis (IOP) have abnormal skeletal microarchitecture and variable tissue-level bone formation rate (BFR). OBJECTIVES: Compare 6 months (M) of teriparatide versus placebo on areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA), bone turnover markers (BTMs) and BFR at 3M by quadruple-labeled transiliac biopsy. Characterize 12M and 24M effects of teriparatide on aBMD and whether BTMs and BFR predict response. DESIGN: 6M phase 2 randomized controlled trial (RCT) followed by open extension. SETTING: Tertiary referral centers. PATIENTS: Premenopausal women with IOP. INTERVENTIONS: A total of 41 women were randomized to either teriparatide 20 mcg (n = 28) or placebo (n = 13). After 6M, those on placebo switched to teriparatide for 24M; those on teriparatide continued for 18M. MAIN OUTCOME MEASURES: 6M RCT: Between-group differences in lumbar spine (LS) aBMD (percent change from baseline), 3M BFR, and hypercalcemia. Open-label extension: Within-group change in LS aBMD over 12M and 24M. Secondary outcomes included aBMD change at other sites and relationship between BTMs, BFR, and changes in aBMD. FINDINGS: Over 6M, LS aBMD increased by 5.5% (95% CI: 3.83, 7.19) in teriparatide and 1.5% (95% CI: −0.73, 3.83) in placebo (P = 0.007). There were increases in 3M BTMs, and BFR (cancellous and endocortical BFR: between-groups P = 0.004). Over 24M, teriparatide increased LS aBMD by 13.2% (95% CI: 10.3, 16.2), total hip by 5.2% (95% CI: 3.7, 6.7) and femoral neck by 5.0% (95% CI: 3.2, 6.7; all P ≤ 0.001). Serum N-terminal propeptides of procollagen type 1 (P1NP) and 3M endocortical BFR were moderately associated with LS aBMD response. Teriparatide was well-tolerated. CONCLUSIONS: Teriparatide increased BFR and formation markers and was associated with marked aBMD improvements in most premenopausal women (82%) with IOP.