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The article presents the study that investigates the close association between bone and vasculature which play a vital role in the regulation of bone remodeling and fracture repair. The researchers found a decrease in bone turnover that lead to a decrease in surfaces covered with remodeling compartments. The reduction of bone remodeling compartment space brought about by antiresorptive therapies reduce the number of skeletal events in advanced cancer.

There is evidence to suggest that restoration of major/rare biominerals by supplementation can produce osteogenic and anti-resorptive effects in humans. LithoLexal® is a natural extract harvested from a marine alga, Lithothamnion sp., with a porous microstructure and multimolecular composition rich in calcium (32% w/w) and magnesium (2.2% w/w) together with ~72 trace bioelements. In vitro, LithoLexal® demonstrated cellular-level osteogenic efficacy through enhancing the maturation and activity of pre-osteoblasts. This extract also expressed the ability to suppress osteoclastogenesis by downregulating the pro-resorptive cytokines TNF-α and IL-1β and the master regulator of inflammation NF-κB. Parathyroid hormone inhibition of parathyroid hormone secretion is another bioactivity of LithoLexal® Bone reported with both short- and long-term administration at a longer duration and higher magnitude than what calcium carbonate could induce. Due to these bioactivities that affect pathogenetic factors of osteoporosis, LithoLexal® Bone is referred to as a disease-modifying adjunctive therapy (DMAT). In postmenopausal animal models, LithoLexal® monotherapy preserved bone mineral density, microarchitecture, and biomechanical properties, while calcium carbonate failed to produce significant outcomes. The pro-resorptive effect of a high-fat diet was also efficiently counteracted in vivo by supplementary LithoLexal®. A large clinical trial on postmenopausal women verified the mitigating effects of LithoLexal® Bone on bone resorption and turnover rate. The characteristic composition of LithoLexal® together with its lattice microstructure are suggested to underlie its in vivo bioactivities. In conclusion, adjunctive therapy with LithoLexal® Bone is an attractive option for clinical prevention and treatment of osteopenia/osteoporosis. [ABSTRACT FROM AUTHOR]

Background. Levels of thyroid-stimulating hormone (TSH) are believed to reflect degree of disease in patients with hypothyroidism, and normalization of levels is the treatment goal. However, despite adequate levels of TSH after starting levothyroxine (LT4) therapy, 5–10% of hypothyroid patients complain of persisting symptoms with a significant negative impact on quality of life. This indicates that TSH is not an optimal indicator of intracellular thyroid hormone effects in all patients. Our aim was to investigate different effects of LT3 and LT4 monotherapy on other biomarkers of the thyroid signaling pathway, in addition to adverse effects, in patients with residual hypothyroid symptoms. Methods. Fifty-nine female hypothyroid patients, with residual symptoms on LT4 monotherapy or LT4/liothyronine (LT3) combination therapy, were randomly assigned in a non-blinded crossover study and received LT4 or LT3 monotherapy for 12 weeks each. Measurements, including serum analysis of a number of biochemical and hormonal parameters, were obtained at the baseline visit and after both treatment periods. Results. Free thyroxine (FT4) was higher in the LT4 group, while free triiodothyronine (FT3) was higher in the LT3 group. The levels of reverse triiodothyronine (rT3) decreased after LT3 treatment compared with LT4 treatment. Both low-density lipoprotein (LDL) and total cholesterol levels were reduced, while sex hormone-binding globulin (SHBG) increased after LT3 treatment compared with LT4 treatment. The median TSH levels for both treatment groups were within the reference range, however, lower in the LT4 group than in the LT3 group. We did not find any differences in pro-B-type natriuretic peptide (NT pro-BNP), handgrip strength, bone turnover markers, or adverse events between the two treatment groups. Conclusion. We have demonstrated that FT4, FT3, rT3, cholesterol, and SHBG show significantly different values on LT4 treatment compared with LT3 treatment in women with hypothyroidism and residual symptoms despite normal TSH levels. No differences in general or bone-specific adverse effects were demonstrated. This trial is registered with NCT03627611 in May 2018. [ABSTRACT FROM AUTHOR]

Roux-en-Y gastric bypass (RYGB) is a common surgical procedure for treatment of morbid obesity. RYGB induces considerable and sustained weight loss, and remission of obesity related-comorbidities. While studies have suggested negative effects of RYGB on bone health, long-term data are lacking. We aimed to evaluate the prevalence of aBMD below the expected range for age, osteopenia, osteoporosis and low-energy fractures in a defined patient cohort 10 years after RYGB. Secondly, we wanted to identify factors associated with increased risk of aBMD z-score or t-score of −1.1 or lower 10 years after RYGB. Patients undergoing RYGB surgery from June 2004 to December 2006 at the Department of Morbid Obesity and Bariatric Surgery, Oslo University Hospital, a tertiary referral centre for treatment of morbid obesity, were invited to a 10 year follow-up. Follow-up visits included morning fasting blood samples, clinical examination, anthropometric measures and dual energy X-ray absorptiometry (DXA). Out of 194 patients eligible for the study, 124 attended the 10 year follow-up and 122 (63%) were examined with DXA. Mean (SD) age was 50.3 (9.0) years, 118 (97%) were of Caucasian ethnicity, 94 were females (77%), of whom 41 (44%) were postmenopausal. Secondary hyperparathyroidism (SHPT) was noted in 37 participants (31%) and vitamin D deficiency (value below 50 nmol/L) and insufficiency (value below 75 nmol/L) in 40 (33%) and 91 (75%), respectively. Among the 63 participants who were premenopausal females or males 49 years or younger the prevalence of areal bone mineral density (aBMD) in the lower range of normal (z-score −1.1- to −1.9) was 30% (n = 19) and aBMD below the expected range for age (z-score ≤ −2.0) was noted in 8% (n = 5). Among the 59 participants who were postmenopausal females or males 50 years or older, the prevalence of osteopenia (t-score −1.1 to −2.4) was 51% (n = 30) and osteoporosis (t-score ≤ −2.5) was 27% (n = 16). The bone resorption markers CTX-1 and PINP were higher in participants with aBMD z-score or t-score of −1.1 or lower compared to participants with aBMD z-score or t-score of −1.0 or higher. Preoperative hypothyroidism, or higher age, postmenopausal status, BMI < 35 kg/m2, SHPT or higher PINP levels at 10 year follow-up were independently associated with aBMD z-score or t-score of −1.1 or lower 10 years after RYGB. Eighteen participants (15%) reported a clinical low-energy fracture after RYGB. In addition, vertebral fracture assessment by DXA revealed that 10 participants (8%) had experienced at least one moderate to severe morphometric vertebral fracture. Ten years after RYGB 27% of postmenopausal females and males 50 years or older were osteoporotic, and 8% of premenopausal females and males 49 years or younger exhibited aBMD below the expected range for age. The prevalence of fragility fractures was high. SHPT, higher age, postmenopausal status or higher PINP levels at 10 years and preoperative hypothyroidism were all independent risk factors for aBMD z-score or t-score of −1.1 or lower 10 years after RYGB. Unlabelled Image • Bone turnover markers were high 10 years after Roux-en-Y gastric bypass (RYGB). • More than one in three had areal bone mineral density (aBMD) scores <90% of expected for age, gender and ethnicity. • Osteopenia, osteoporosis and low energy fractures were frequent. [ABSTRACT FROM AUTHOR]

Summary: Objective: The high prevalence of secondary hyperparathyroidism (SHPT) after obesity surgery is a concern for long‐term bone health. Limited knowledge exists about optimal vitamin D and suppression of parathyroid hormone (PTH) after these procedures. The aim of this study was to investigate the prevalence of SHPT and its relation to vitamin D status. Design: A cross‐sectional study at Oslo University Hospital, Norway. Patients: A total of 502 consecutive patients, age 22‐64 years, attending 2‐year follow‐up after Roux‐en‐Y gastric bypass. Measurements: A serum intact PTH >7.0 pmol/L in the absence of elevated serum ionized calcium (iCa) was considered as SHPT. Vitamin D status was defined by serum concentrations of 25‐hydroxyvitamin D (S‐25(OH)D). Results: Altogether, 171 patients (34%) had SHPT. The prevalence of SHPT varied across the range of S‐25(OH)D (P < 0.001), being highest (71%) with S‐25(OH)D < 25 nmol/L. Compared with S‐25(OH)D < 50 nmol/L, the prevalence of SHPT was lower with S‐25(OH)D ≥ 50 nmol/L (29.0%; RR = 0.64 (95%‐CI:0.50‐0.81)) and S‐25(OH)D ≥ 75 nmol/L (27.7%; RR = 0.61 (95%‐CI:0.44‐0.84)). S‐25(OH)D ≥ 100 nmol/L was associated with the lowest PTH and the lowest prevalence of SHPT (16.0%; RR = 0.35 (95%‐CI:0.14‐0.88) compared with S‐25(OH)D < 50 nmol/L) and the most normal calcium distribution. These associations were most pronounced with iCa in the lower range. A synergistic association was found for S‐25(OH)D and iCa on SHPT. Conclusions: Vitamin D deficient patients had the highest prevalence of SHPT 2 years after gastric bypass. PTH and the prevalence of SHPT were notably lower with S‐25(OH)D ≥ 100 nmol/L, compared with lower target levels. [ABSTRACT FROM AUTHOR]

Introduction The optimal duration of osteoporosis treatment is controversial. As opposed to bisphosphonates, denosumab does not incorporate into bone matrix and bone turnover is not suppressed after its cessation. Recent reports imply that denosumab discontinuation may lead to an increased risk of multiple vertebral fractures. Methods The European Calcified Tissue Society (ECTS) formed a working group to perform a systematic review of existing literature on the effects of stopping denosumab and provide advice on management. Results Data from phase 2 and 3 clinical trials underscore a rapid decrease of bone mineral density (BMD) and a steep increase in bone turnover markers (BTMs) after discontinuation of denosumab. Clinical case series report multiple vertebral fractures after discontinuation of denosumab and a renewed analysis of FREEDOM and FREEDOM Extension Trial suggests, albeit does not prove, that the risk of multiple vertebral fractures may be increased when denosumab is stopped due to a rebound increase in bone resorption. Conclusion There appears to be an increased risk of multiple vertebral fractures after discontinuation of denosumab although strong evidence for such an effect and for measures to prevent the occurring bone loss is lacking. Clinicians and patients should be aware of this potential risk. Based on available data, a re-evaluation should be performed after 5 years of denosumab treatment. Patients considered at high fracture risk should either continue denosumab therapy for up to 10 years or be switched to an alternative treatment. For patients at low risk, a decision to discontinue denosumab could be made after 5 years, but bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover. However, since the optimal bisphosphonate regimen post-denosumab is currently unknown continuation of denosumab can also be considered until results from ongoing trials become available. Based on current data, denosumab should not be stopped without considering alternative treatment in order to prevent rapid BMD loss and a potential rebound in vertebral fracture risk. [ABSTRACT FROM AUTHOR]

The aim of the study was to test, whether bone material strength differs between different subtypes of osteoporotic fracture and assess whether it relates to vertebral fracture severity. Cortical bone material strength index (BMSi) was measured by impact microindentation in 66 women with osteoporotic fracture and 66 age- and sex-matched controls without fracture. Bone mineral density (BMD) and bone turnover markers were also assessed. Vertebral fracture severity was graded by semiquantitative (SQ) grading. Receiver operator characteristic (ROC) curves were used to examine the ability of BMSi to discriminate fractures. Subjects with osteoporotic fractures exhibited lower BMSi than controls (71.5 ± 7.3 vs. 76.4 ± 6.2, p < 0.001). After adjusting for age and hip BMD, a significant negative correlation was seen between BMSi and vertebral fracture severity (r 2 = 0.19, p = 0.007). A decrease of one standard deviation (SD) in BMSi was associated with increased risk of fracture (OR 2.62; 95% CI 1.35, 5.10, p = 0.004). ROC curve areas under the curve (AUC) for BMSi in subjects with vertebral fracture (VF), hip fracture (HF), and non-vertebral non-hip fracture (NVNHFx), (mean; 95% CI) were 0.711 (0.608; 0.813), 0.712 (0.576; 0.843), 0.689 (0.576; 0.775), respectively. Combining BMSi and BMD provided further improvement in the discrimination of fractures with AUC values of 0.777 (0.695; 0.858), 0.789 (0.697; 0.882), and 0.821 (0.727; 0.914) for VFx, HFx, and NVNHFx, respectively. Low BMSi of the tibial cortex is associated with increased risk of all osteoporotic fractures and severity of vertebral fractures. [ABSTRACT FROM AUTHOR]

Low-grade inflammation is associated with fractures, while the relationship between inflammation and bone mineral density (BMD) is less clear. Moreover, any gender differences in the sensitivity to inflammation are still poorly elucidated. We therefore tested the hypothesis that high-sensitivity C-reactive protein (CRP) is an independent risk factor for low BMD and non-vertebral fractures, in both genders, and whether there are gender differences in these associations. CRP levels and BMD at the total hip and femoral neck were measured in 1902 women and 1648 men between 55 and 74 years of age, at baseline in the Tromsø Study, Norway, in 2001–2002. Non-vertebral fractures were registered from hospital X-ray archives during an average of 7.2 years follow-up. Linear regression analyses were used for CRP association with BMD and Cox proportional hazards model for fracture prediction by CRP. During 25 595 person-years follow-up, 366 (19%) women and 126 (8%) men suffered a non-vertebral fracture. There was no association between CRP and BMD in women, but an inverse association in men ( p = 0.001) after adjustment for age and body mass index. Each standard deviation (SD) increase in log-CRP was associated with an increased risk for non-vertebral fracture by 13% in women and 22% in men (hazard ratios (HRs) 1.13, 95% confidence interval (CI) 1.02–1.26, p = 0.026 and 1.22, 95% CI = 1.00–1.48, p = 0.046, respectively). After adjustment for BMD and other risk factors, women with CRP in the upper tertile exhibited 39% higher risk for fracture than those in the lowest tertile of CRP (HR = 1.39, 95% CI = 1.06–1.83, p = 0.017), while men in the upper tertile exhibited 80% higher risk (HR = 1.80, 95% CI = 1.10–2.94, p = 0.019). In summary, CRP was not associated with BMD in women but inversely associated in men, and predicted fractures in both genders. We infer that inflammation influence fracture risk in both women and men, although the biological mechanisms may differ between the genders. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that the administration of zoledronic acid (ZOL) once yearly for 3 years or once over 3 years, yields similar antifracture efficacy. Bone turnover markers can predict the antifracture efficacy of antiresorptive agents, with procollagen type 1 N-terminal propeptide (P1NP) being the most useful marker. In this retrospective cohort study, we explored the effects of intravenous dosing of ZOL guided by serum (S)-P1NP assessment on bone mineral density (BMD) and fractures. Consenting patients ( N  = 202, mean age 68.2 years) with osteoporosis were treated with ZOL for an average of 4.4 (range 2-8) years. S-P1NP and BMD were measured at baseline and every 1-2 years. We assessed the number of subsequent vertebral and nonvertebral fractures in the 2-year time periods. The number of patients assessed was 202, 147, 69, and 29 at years 1-2, 3-4, 5-6, and 7-8, respectively. A new ZOL infusion was given if S-P1NP exhibited values above 35 μg/L. BMD increased by 6.2% (SD 4.0) over the first 2 years and stabilized in years 2-8 ( P  <.05). Median S-P1NP exhibited an initial reduction from 58.0 to 31.3 μg/L at year 2 and then increased to 39.0 μg/L at years 7-8. Compared with fractures observed in the last 2 years before baseline, fracture rates exhibited consistent reductions, for vertebral fractures odds ratio (OR) [95% confidence interval] = 0.61 [0.47, 0.80], P  <.001 and for nonvertebral fractures OR = 0.23 [0.18, 0.31], P  <.001. In conclusion, intermittent dosing of intravenous ZOL based on the assessment of S-P1NP with cut-off at 35 μg/L resulted in an initial increase followed by a stable BMD, suppression of S-P1NP, and stable reduction of fractures for 8 years. Only 39% of patients needed more than one infusion. This approach reduces healthcare costs and might also reduce the risk of rare side effects such as osteonecrosis of the jaw and atypical femoral fracture., Competing Interests: T.T.B. reports speaker fees from UCB, Amgen, Roche Diagnostics, and Pharma Prim. Advisory board for UCB. S.L.Ø. reports speaker fees from Novo Nordisk and Eli Lilly and is on the advisory board for Helseresepten. B.F.E.: none. E.F.E. reports consultant fees from UCB, Amgen, Gilead, and Pharma Medico, and honoraria from Amgen, Gedon Richter, and Novo Nordisk. Study support from Roche Diagnostics., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Background: Bone turnover markers (BTMs) have emerged as a useful tool for monitoring bone remodeling activity in the skeleton, and their serum levels correlate with bone loss rates in osteoporotic and normal individuals. Whether the same holds for other metabolic bone diseases is still subject to discussion., Methods: We analyzed the relation between levels of BTMs and TSH in 79 females on thyroid hormone substitution therapy for hypothyroidism. Based on the reference range for TSH (0.2-4.0 mU/L) in our lab, we assessed BTMs in five different groups of patients based on the following criteria: (1) hypothyroidism (TSH >4.0); (2) TSH in the high normal range (1.0-4.0); (3) TSH in the low normal range (0.2-1.0); (4) TSH below the normal range (0.01-0.2); (5) TSH undetectable (<0.01). We studied the relationship between TSH and four different bone markers: procollagen type 1 N-terminal propeptide (PINP), C-terminal cross-linking telopeptide of type 1 collagen (CTX), osteocalcin (OC), and bone specific alkaline phosphatase (BSAP). In a subgroup of patients, bone mineral density was assessed by a DXA scan., Results: PINP emerged as the most sensitive and dynamic BTM for assessment of bone turnover in this patient group, achieving significant rho values on nonparametric correlation analysis for both TSH (rho -0.47; p =0.0001) and FT4 (rho 0.27; p =0.018). CTX and OC also revealed significant correlations to TSH, albeit with lower rho values (-0.37 and -0.24, respectively). Categorical analysis showed that bone turnover increased significantly, albeit with pronounced interindividual variability for TSH values below the lower limit of normal (0.2 mU/l), with the most severe affected being women exhibiting suppression of TSH. Further analysis of loss rates by DXA in a limited subgroup of patients showed that this was accompanied by accelerated bone loss., Conclusion: PINP is the most sensitive marker of bone turnover in thyroid disorders. TSH values below the lower limit of normal are associated with increased bone turnover and accelerated bone loss, however, with pronounced interindividual variations. Assessment of PINP may be a valuable tool in cases where there is concern about possible adverse effects of thyroid hormone substitution therapy on bone., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Betty Ann Bjerkreim et al.)

Objective: The effects of levothyroxine (LT4)/liothyronine (LT3) combination therapy on quality of life (QoL) in hypothyroid patients former on LT4 monotherapy have been disappointing. We therefore wanted to test the effects of LT3 monotherapy on QoL in hypothyroid patients with residual symptoms despite thyroid stimulating hormone (TSH) values within the reference range., Design: Female hypothyroid patients with residual symptoms on LT4 monotherapy or combination LT4/LT3 therapy received LT3 and LT4 monotherapy, respectively for 12 weeks in a non-blinded randomized crossover study., Methods: Fifty-nine patients aged 18-65 years were included. QoL was assessed using one disease-specific questionnaire (ThyPRO) and two generic questionnaires (Fatigue Questionnaire and SF-36) at baseline and at the end of the two treatment periods. Clinical indices of cardiovascular health (resting heart rate and blood pressure), as well as thyroid tests, were assessed at baseline and at the end of the two treatment periods., Results: After 12 weeks of LT3 treatment, 12 of the 13 domains of the ThyPRO questionnaire (physical, mental and social domains) showed significant improvements. The most pronounced improvements were less tiredness (mean -21 ± 26; P <0.0001) and cognitive complaints (mean -20 ± 20; P <0.0001). LT4 monotherapy exerted minor effects on two domains only (cognitive complaints and impaired daily life). All three dimensions' scores in the Fatigue Questionnaire (physical, mental and total fatigue) improved after LT3 treatment compared to baseline ( P <0.001), and in the SF-36 questionnaire 7 of 8 scales showed significantly better scores after LT3 treatment compared to baseline. There were no differences in blood pressure or resting heart rate between the two treatment groups. TSH in patients on LT3 was slightly higher (median 1.33 mU/L (interquartile range (IQR) 0.47-2.26)) than in patients on LT4 (median 0.61 mU/L (IQR 0.25-1.20; P <0.018). Five patients on LT3 dropped out of the study due to subjectively reported side effects, compared to only one on LT4., Conclusions: LT3 treatment improved QoL in women with residual hypothyroid symptoms on LT4 monotherapy or LT4/LT3 combination therapy. Short-term LT3 treatment did not induce biochemical or clinical hyperthyroidism, and no cardiovascular adverse effects were recorded. Further studies are needed to assess the long-term safety and efficacy of LT3 monotherapy., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03627611., Competing Interests: Authors SSH and EFE were employed by Pilestredet Park Specialist Center and LJO was employed by Balderklinikken. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2022 Bjerkreim, Hammerstad, Gulseth, Berg, Omdal, Lee-Ødegård and Eriksen.)

Modern advances in molecular medicine have led to the reframing of osteoarthritis as a metabolically active, inflammatory disorder with local and systemic contributing factors. According to the 'inflammatory theory' of osteoarthritis, immune response to an initial damage is the key trigger that leads to progressive joint destruction. Several intertwined pathways are known to induce and govern articular inflammation, cartilage matrix degradation, and subchondral bone changes. Effective treatments capable of halting or delaying the progression of osteoarthritis remain elusive. As a result, supplements such as glucosamine and chondroitin sulphate are commonly used despite the lack of scientific consensus. A novel option for adjunctive therapy of osteoarthritis is LithoLexal ® Joint, a marine-derived, mineral-rich extract, that exhibited significant efficacy in clinical trials. LithoLexal ® has a lattice microstructure containing a combination of bioactive rare minerals. Mechanistic research suggests that this novel treatment possesses various potential disease-modifying properties, such as suppression of nuclear factor kappa-B, interleukin 1β, tumor necrosis factor α, and cyclooxygenase-2. Accordingly, LithoLexal ® Joint can be considered a disease-modifying adjunctive therapy (DMAT). LithoLexal ® Joint monotherapy in patients with knee osteoarthritis has significantly improved symptoms and walking ability with higher efficacy than glucosamine. Preliminary evidence also suggests that LithoLexal ® Joint may allow clinicians to reduce the dose of nonsteroidal anti-inflammatory drugs in osteoarthritic patients by up to 50%. In conclusion, the multi-mineral complex, LithoLexal ® Joint, appears to be a promising candidate for DMAT of osteoarthritis, which may narrow the existing gap in clinical practice.

Background: Thyroid hormones are essential for the full thermogenic response of brown adipose tissue (BAT) and have been implicated in dermal temperature regulation. Nevertheless, persistent cold-intolerance exists among a substantial proportion of hypothyroid patients on adequate levothyroxine (LT4) substitution., Materials and Methods: To assess if skin temperature and activation of BAT during treatment with liothyronine (LT3) differs from that of LT4 treatment, fifty-nine female hypothyroid patients with residual symptoms on LT4 or LT4/LT3 combination therapy were randomly assigned in a non-blinded crossover study to receive monotherapy with LT4 or LT3 for 12 weeks each. Change in supraclavicular (SCV) skin temperature overlying BAT, and sternal skin temperature not overlying BAT, during rest and cold stimulation were assessed by infrared thermography (IRT). In addition, abundance of exosomal miR-92a, a biomarker of BAT activation, was estimated as a secondary outcome., Results: Cold stimulated skin temperatures decreased less with LT3 vs . LT4 in both SCV (mean 0.009°C/min [95% CI: 0.004, 0.014]; P <0.001) and sternal areas (mean 0.014°C/min [95% CI: 0.008, 0.020]; P <0.001). No difference in serum exosomal miR-92a abundance was observed between the two treatment groups., Conclusion: LT3 may reduce dermal heat loss. Thermography data suggested increased BAT activation in hypothyroid patients with cold-intolerance. However, this finding was not corroborated by assessment of the microRNA biomarker of BAT activation., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03627611., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bjerkreim, Hammerstad, Gulseth, Berg, Lee-Ødegård, Rangberg, Jonassen, Budge, Morris, Law, Symonds and Eriksen.)

Objective: Type 1 diabetes (T1D) is associated with substantial fracture risk. Bone mineral density (BMD) is, however, only modestly reduced, suggesting impaired bone microarchitecture and/or bone material properties. Yet, the skeletal abnormalities have not been uncovered. Men with T1D seem to experience a more pronounced bone loss than their female counterparts. Hence, we aimed to examine different aspects of bone quality in men with T1D., Design and Methods: In this cross-sectional study, men with T1D and healthy male controls were enrolled. BMD (femoral neck, total hip, lumbar spine, whole body) and spine trabecular bone score (TBS) were measured by dual x-ray absorptiometry, and bone material strength index (BMSi) was measured by in vivo impact microindentation. HbA1c and bone turnover markers were analyzed., Results: Altogether, 33 men with T1D (43 ± 12 years) and 28 healthy male controls (42 ± 12 years) were included. Subjects with T1D exhibited lower whole-body BMD than controls (P = 0.04). TBS and BMSi were attenuated in men with T1D vs controls (P = 0.016 and P = 0.004, respectively), and T1D subjects also had a lower bone turnover. The bone parameters did not differ between subjects with or without diabetic complications. Duration of disease correlated negatively with femoral neck BMD but not with TBS or BMSi., Conclusions: This study revealed compromised bone material strength and microarchitecture in men with T1D. Moreover, our data confirm previous studies which found a modest decrease in BMD and low bone turnover in subjects with T1D. Accordingly, bone should be recognized as a target of diabetic complications.

Osteoarthritis (OA) is affecting large proportions of the population worldwide. So far, no effective disease modifying drug has been developed for this disease, limiting the therapeutic options to pain medications, physiotherapy and ultimately surgical approaches, mainly joint implant surgery. In vitro and animal studies have demonstrated that bisphosphonates have the potential to become effective modalities for the treatment of OA. This group of pharmacological agents modulates crucial aspects of OA pathogenesis (subchondral bone turnover and loss, bone marrow edema formation, cartilage degeneration and synovitis), and have shown clear efficacy in animal models of OA. Human studies have, however, so far been disappointing with only one of six clinical studies showing clear short-term efficacy. Possible reasons for these discrepancies will be discussed., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: Secondary hyperparathyroidism (SHPT) after obesity surgery may affect bone health. Optimal vitamin D levels have not been established to prevent SHPT postoperatively. We investigated whether SHPT differed across threshold levels of serum 25-hydroxyvitamin D (S-25(OH)D) from 6 months up to 5 years after Roux-en-Y gastric bypass (RYGB)., Materials and Methods: We included 554 patients at follow-up 5 years postoperatively. Blood samples were analysed for S-25(OH)D, ionized calcium (iCa) and parathyroid hormone (PTH) during follow-up., Results: PTH and prevalence of SHPT increased from 6 months to 5 years postoperatively, while S-25(OH)D and iCa decreased (all P < 0.001). PTH and SHPT development are related with S-25(OH)D, and PTH differed between all subgroups of S-25(OH)D. SHPT occurred less frequently across all subgroups of S-25(OH)D ≥ 50 nmol/l during follow-up: odds ratio (OR) 0.44 (95% CI 0.36-0.54) in patients with S-25(OH)D ≥ 50 nmol/l, OR 0.38 (0.30-0.49) with S-25(OH)D ≥ 75 nmol/l and OR 0.19 (0.12-0.31) with S-25(OH) D ≥ 100 nmol/l, all compared with S-25(OH)D < 50 nmol/l. At 5 years, 208/554 patients (38%) had SHPT; SHPT was found in 94/188 patients (50%) with S-25(OH)D < 50 nmol/l, in 69/222 (31%) with S-25(OH)D 50-74 nmol/l, in 40/117 (34%) with S-25(OH)D 75-99 nmol/l and in 5/27 (19%) with S-25(OH)D ≥ 100 nmol/l. An interaction existed between S-25(OH)D and iCa. Bone alkaline phosphatase remained increased with SHPT., Conclusions: A significant relationship existed between S-25(OH)D and development of PTH and SHPT. The prevalence of SHPT was lower with threshold levels 25(OH)D ≥ 50 nmol/l and ≥ 75 nmol/l over the 5 years, and lowest with S-25(OH)D ≥ 100 nmol/l.

Background: Several guidelines have been reported for bone-directed treatment in women with early breast cancer (EBC) for averting fractures, particularly during aromatase inhibitor (AI) therapy. Recently, a number of studies on additional fracture related risk factors, new treatment options as well as real world studies demonstrating a much higher fracture rate than suggested by randomized clinical controlled trials (RCTs). Therefore, this updated algorithm was developed to better assess fracture risk and direct treatment as a position statement of several interdisciplinary cancer and bone societies involved in the management of AI-associated bone loss (AIBL)., Patients and Methods: A systematic literature review identified recent advances in the management of AIBL. Results with individual agents were assessed based on trial design, size, follow-up, and safety., Results: Several fracture related risk factors in patients with EBC were identified. Although, the FRAX algorithm includes fracture risk factors (RF) in addition to BMD, it does not seem to adequately address the effects of AIBL. Several antiresorptive agents can prevent and treat AIBL. However, concerns regarding compliance and long-term safety remain. Overall, the evidence for fracture prevention is strongest for denosumab 60 mg s.c. every 6 months. Additionally, recent studies as well as an individual patient data meta-analysis of all available randomized trial data support additional anticancer benefits from adjuvant bisphosphonate treatment in postmenopausal women with a 34% relative risk reduction in bone metastasis and 17% relative risk decrease in breast cancer mortality that needs to be taken into account when advising on management of AIBL., Conclusions: In all patients initiating AI treatment, fracture risk should be assessed and recommendation with regard to exercise and calcium/vitamin D supplementation given. Bone-directed therapy should be given to all patients with a T-score<-2.0 or with a T-score of <-1.5 SD with one additional RF, or with ≥2 risk factors (without BMD) for the duration of AI treatment. Patients with T-score>-1.5 SD and no risk factors should be managed based on BMD loss during the first year and the local guidelines for postmenopausal osteoporosis. Compliance should be regularly assessed as well as BMD on treatment after 12 - 24 months. Furthermore, because of the decreased incidence of bone recurrence and breast cancer specific mortality, adjuvant bisphosphonates are recommended for all postmenopausal women at significant risk of disease recurrence.