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Collagen peptides (CPs) have been shown to potentially have a role as a treatment option in osteopenia. In the present randomized prospective study, we examined the effect of calcium, vitamin D with and without CPs supplementation on changes in volumetric bone mineral density (vBMD) and bone geometry assessed by peripheral quantitative computed tomography at the tibia, areal bone mineral density (aBMD) assessed by dual-energy X-ray absorptiometry at the lumbar spine and the hip and bone turnover markers over 12-mo. Fifty-one postmenopausal women with osteopenia were allocated to Group A who received orally 5 g CPs, 500 mg calcium and 400 IU vitamin D3 and Group B who received the same dose of calcium and vitamin D3 per day. The primary endpoint was the change of trabecular bone mineral content (BMC) and vBMD after 12-mo supplementation in Groups A and B. At the trabecular site (4% of the tibia length), Group A had a significant increase of total BMC by 1.96 ± 2.41% and cross-sectional area by 2.58 ± 3.91%, trabecular BMC by 5.24 ± 6.48%, cross-sectional area by 2.58 ± 3.91% and vBMD by 2.54 ± 3.43% and a higher % change of these parameters at 12 mo in comparison to Group B (p0.01, p = 0.04, p0.01, p = 0.04, p = 0.02, respectively). At the cortical site (38% of the tibia length), total and cortical vBMD increased by 1.01 ± 2.57% and 0.67 ± 1.71%. Furthermore, the mean aBMD at the spine was higher (p = 0.01), while bone markers decreased in Group A compared to Group B. The present study shows improvement of trabecular and cortical parameters as assessed by peripheral quantitative computed tomography at the tibia, prevention of aBMD decline and decrease of bone turnover after 12-mo supplementation with calcium, vitamin D with CPs.

Denosumab discontinuation results in rapid bone loss and increased risk of multiple rebound-associated vertebral fractures (RAVFs). The optimal treatment for patients who have sustained such fractures is currently unknown. We aimed to investigate the bone mineral density (BMD) changes achieved with various regimens in postmenopausal women who had sustained RAVFs after denosumab discontinuation in everyday clinical practice. In this multicenter, retrospective observational study, 39 Greek postmenopausal women from six regional bone centers throughout Greece with RAVFs after denosumab discontinuation were included. We collected BMD and fracture data before and 1 year after treatment with denosumab (n = 20), teriparatide (n = 8), zoledronate (n = 8) or teriparatide/denosumab combination (n = 3). Both lumbar spine (LS)-- and femoral neck (FN)-BMD were preserved with all regimens used. With the exception of zoledronate, a trend towards increase was observed with all regimens in LS-BMD. Three patients sustained additional fractures despite treatment reinstitution (2 with zoledronate and 1 with teriparatide). Among patients with RAVFs following denosumab discontinuation both antiresorptive (zoledronate and denosumab) and anabolic (teriparatide) treatment as well as the combination of denosumab with teriparatide seem to be effective in terms of BMD response.

Adults with β- thalassemia major (β-TM) develop low BMD and fragility fractures at a higher incidence and at a younger age compared to the general population. The disease itself, including direct effects of anemia and iron overload toxicity on bone turnover, genetic susceptibility, thalassemia-related endocrinopathies and acquittance of suboptimal peak bone mass contribute to low bone mass and increased bone fragility frequently encountered among these patients. Current management of osteoporosis requires long-term treatment that can be provided by agents that reduce the risk of all osteoporotic fractures by modulating bone metabolism with different mechanisms of action. These include inhibitors of bone remodeling (e.g., bisphosphonates, denosumab) and stimulators of bone formation (e.g., PTHR1 agonists and sclerostin antibodies). Considering the unique characteristics of osteoporosis associated with β-TM and the clinical importance of balancing the risk/benefit of treatment in the long-term, appropriate use of these therapeutic approaches is essential for patient care. In this review we outline current literature on the use of anti-osteoporotic drugs in β-TM patients with osteoporosis focusing on data on the efficacy, safety, and duration of treatment. In addition, we propose a long-term management plan for β-TM -associated osteoporosis aiming at the optimal patient care for this special population.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare disease, presenting in most cases with severe back pain due to low energy vertebral fractures (VFs). Our purpose was to assess the effect of teriparatide (TPTD) vs. conventional management on areal bone mineral density (aBMD) and trabecular bone score (TBS) in patients with PLO. A multicenter retrospective cohort study concerning premenopausal women with PLO. Nineteen women were treated with TPTD (20 μg/day) (group A) plus calcium and vitamin D and eight women with calcium and vitamin D only (group B) for up to 24 months. The primary end-point was between group differences in lumbar spine (LS) and total hip (TH) aBMD, and TBS at 12 and 24 months. Patients in group A had sustained a median of 4.0 VFs (3–9) vs. 2.5 VFs (1–10) in group B (p = 0.02). At 12 months, patients on TPTD vs. controls achieved a mean aBMD increase of 20.9 ± 11.9% vs. 6.2 ± 4.8% at the LS (p

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.

Primary hyperparathyroidism (PHPT) is one of the most common endocrine disorders characterized by parathyroid hormone (PTH)-dependent hypercalcemia. Cardinal features include low trauma fractures, nephrolithiasis, and chronic kidney disease. Several experimental studies established that parathyroid hormone exerts actions on the cardiovascular (CV) system, including vasodilatation and positive inotropic and chronotropic effects. Observational studies, especially in severe cases, report a higher prevalence of hypertension, diabetes mellitus, lipid abnormalities, endothelial dysfunction, arrhythmias, and left ventricular hypertrophy in patients with PHPT, while the risk of CV events seems to be increased in severe cases. However, the effect of surgery is inconsistent on CV abnormalities and, more importantly, on CV disease (CVD) events, especially in mild cases. In the current review, we describe the available evidence linking PHPT and CVD, as well as the effect of surgical management and pharmacological treatment on CVD manifestations in patients with PHPT. Based on the current evidence, CVD is not considered an indication for surgery.

Hypophosphatasia (HPP) is an inherited metabolic disease caused by loss-of-function mutations in the tissue non-specific alkaline phosphatase (TNAP) gene. Reduced activity of TNAP leads to the accumulation of its substrates, mainly inorganic pyrophosphate and pyridoxal-5′-phosphate, metabolic aberrations that largely explain the musculoskeletal and systemic features of the disease. More than 400 ALPL mutations, mostly missense, are reported to date, transmitted by either autosomal dominant or recessive mode. Severe disease is rare, with incidence ranging from 1:100,000 to 1:300,000 live births, while the estimated prevalence of the less severe adult form is estimated to be between 1:3100 to 1:508, in different countries in Europe. Presentation largely varies, ranging from death in utero to asymptomatic adults. In infants and children, clinical features include skeletal, respiratory and neurologic complications, while recurrent, poorly healing fractures, muscle weakness and arthropathy are common in adults. Persistently low serum alkaline phosphatase is the cardinal biochemical feature of the disease. Management requires a dedicated multidisciplinary team. In mild cases, treatment is usually symptomatic. Severe cases, with life-threating or debilitating complications, can be successfully treated with enzyme replacement therapy with asfotase alfa.

Rebound-associated vertebral fractures (RAVFs) could occur in a minority of the patients who discontinue denosumab. In such patients, denosumab is often reinstituted to rapidly suppress bone turnover and avert the risk of additional fractures. Herein we report the cases of 2 patients who sustained RAVFs, and in whom resuming denosumab treatment did not avert the occurrence of new RAVFs a few months later, despite the suppression of bone turnover markers. It seems that denosumab reinstitution cannot completely eliminate the risk of new RAVFs and that the rebound of bone turnover may not be the sole mechanism to explain this phenomenon.

This randomized controlled trial investigated the effects of a 5-month high-intensity hybrid-type neuromuscular training program with nontraditional implements on cardiometabolic health, redox status, and cardiovascular disease (CVD) risk in inactive overweight and obese women. Forty-nine inactive female participants with overweight and obesity (age: 36.4 ± 4.4 years, BMI: 29.1 ± 2.9 kg/m2) were randomly assigned to either a control (C, n = 21) or a training group (TR, n = 28). TR followed a 20-week supervised, progressive, time-efficient (3 days/week, 6–15 min net exercise time) program implementing loaded fundamental movement patterns with prescribed work-to-rest time intervals (20–40 s, 1:2, 1:1, 2:1) in a circuit fashion (2–3 rounds). Cardiometabolic risk factors were measured at baseline and post-training as secondary outcomes of a larger randomized controlled trial. At post-intervention, TR demonstrated favorable changes in resting heart rate (−7%, p = 0.043), high-density lipoprotein (+18.1%, p = 0.029), atherogenic index (−17%, p = 0.045), mean arterial pressure (−4.5%, p = 0.03), waist circumference (−6.2%, p = 0.005), waist-to-hip ratio (−4.6%, p = 0.015), metabolic syndrome severity score (−222%, p = 0.024), full 30-year CVD risk (−15.8%, p = 0.002) and hard 30-year CVD risk (−17.6%, p = 0.01), vascular age (−7.8%, p = 0.002), protein carbonyls (−45.7%, p = 0.001), catalase activity (+15.2%, p = 0.023), and total antioxidant capacity (+11.4%, p = 0.002) relative to C. Additionally, TR induced beneficial changes in fasting glucose (−3.4%, p = 0.002), homeostatic model assessment for insulin resistance (−15.7%, p &lt, 0.001), diastolic blood pressure (−5.6%, p &lt, 0.001), reduced glutathione (+39.8%, p &lt, 0.001), 10-year CVD risk (−17.4%, p = 0.011), and total bilirubin (−21.7%, p &lt, 0.001) compared to baseline. These results suggest that hybrid-type neuromuscular training may improve aspects of cardiometabolic health and antioxidant status in inactive overweight and obese women providing a time-efficient (~100 min/week) exercise approach in a real-world gym setting.

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.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare disease, presenting in most cases with severe back pain due to low energy vertebral fractures (VFs). Our purpose was to assess the effect of teriparatide (TPTD) vs. conventional management on areal bone mineral density (aBMD) and trabecular bone score (TBS) in patients with PLO. A multicenter retrospective cohort study concerning premenopausal women with PLO. Nineteen women were treated with TPTD (20 μg/day) (group A) plus calcium and vitamin D and eight women with calcium and vitamin D only (group B) for up to 24 months. The primary end-point was between group differences in lumbar spine (LS) and total hip (TH) aBMD, and TBS at 12 and 24 months. Patients in group A had sustained a median of 4.0 VFs (3-9) vs. 2.5 VFs (1-10) in group B (p = 0.02). At 12 months, patients on TPTD vs. controls achieved a mean aBMD increase of 20.9 ± 11.9% vs. 6.2 ± 4.8% at the LS (p 0.001), 10.0 ± 11.6% vs. 5.8 ± 2.8% at the TH (p = 0.43), and 6.7 ± 6.9% vs. 0.9 ± 3.7% in TBS (p = 0.09), respectively. At 24 months, seven patients on TPTD and six controls achieved a mean LS aBMD increase of 32.9 ± 13.4% vs. 12.2 ± 4.2% (p = 0.001). P1NP levels during the first month of TPTD treatment were positively correlated with the 1-year LS aBMD change (r = 0.68, p = 0.03). No new clinical fractures occurred while on-treatment. In patients with PLO, TPTD treatment resulted in significantly greater increases in LS aBMD compared with calcium and vitamin D supplementation at 12 and 24 months.

Background/Aim: Postsurgical hypoparathy-roidism (PostHypo) is a common complication after total thyroidectomy. We studied the risk factors associated with PostHypo. Patients and Methods: The study included 109 women, (mean age: 50.7±10.75 years), who underwent total thyroidectomy for thyroid diseases. Results: Based on the development of biochemical hypocalcemia on the first postoperative day following total thyroidectomy, (cCa

Derangements in phosphate and calcium homeostasis are common in patients with beta-thalassemia. Fibroblast growth factor 23 (FGF23) is among the main hormones regulating phosphate levels, while several studies underline an interplay between iron (Fe) and FGF23. Herein, we investigated, for the first time, the serum intact molecule (iFGF23) and the carboxyl-terminal fragment (C-FGF23) and Klotho levels simultaneously in patients with beta-thalassemia major receiving iron chelation regimens in comparison to healthy control subjects. We also correlated them with the body iron burden. The observational case-control study included 81 subjects (40 thalassemic patients and 41 healthy controls). Serum iFGF23, C-FGF23 and Κlotho were measured by ELISA. Parathormone, 25-hydroxycholecalciferol, calcium, and phosphorus were measured in blood and/or urine. The degree of hemosiderosis was evaluated by assessing the serum ferritin levels and performing T2* MRI measurements. Serum C-FGF23 levels were significantly lower in patients compared to control subjects (p=0.04), while iFGF23 and Klotho levels did not differ. Serum C-FGF23 levels were negatively correlated with ferritin (r=–0,421, p=0.018), whereas there were no significant correlations of each of the three factors with the iron chelation therapy. Decreased serum C-FGF23 levels were found in βTh patients which may be attributed to inhibition of proteolytic cleavage of iFGF23. Further studies in a greater number of patients will shed more light on the disturbances of the iFGF23, Klotho and C-FGF23 in thalassemia and their possible role in bone disease of such patients.

The Bone Section of the Hellenic Endocrine Society has issued the recommendations herein presented with the aim of providing guidance on optimal management of patients with parathyroid disorders in everyday clinical practice within the Greek health care setting. Although the methodology followed to formulate these recommendations was not strictly based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principles, they were drawn up after an extensive review of the literature and of the currently available guidelines for the management of parathyroid disorders worldwide. Specifically for primary hyperparathyroidism (PHPT), the 2011 guidelines of the Greek National Organization of Medicines were updated accordingly. In particular, definitions, etiologies, and recommended and optional laboratory and imaging examinations are provided both for PHPT and chronic hypoparathyroidism (HypoPT). Finally, treatment algorithms are provided for the management of both PHPT and HypoPT. Specifically for HypoPT, the treatment algorithm describes the recommended steps that should be followed to achieve optimal management of chronic hypocalcemia and the complications of HypoPT through the conventional treatment available in Greece and the use of recombinant human PTH(1-84).

Objectives: Collagen peptides (CPs) seem to exert beneficial effects on bone and may have a role as a treatment option. In the present randomized prospective study, we aimed to examine the efficacy, as expressed by changes in P1NP and CTX, and the tolerability of 3-month supplementation of calcium, vitamin D with or without bioactive CPs in postmenopausal women with osteopenia. Methods: Fifty-one female, postmenopausal women with osteopenia were allocated to two groups: Group A received a sachet containing 5 g CPs, 3.6 g calcium lactate (equivalent to 500 mg of elemental calcium) and 400 IU vitamin D3 and group B received a chewable tablet containing 1.25 g calcium carbonate (equivalent to 500 mg of elemental calcium) and 400 IU vitamin D3 daily. Results: In group A, the P1NP levels significantly decreased by 13.1% (p

Homozygous beta-thalassemia represents a serious hemoglobinopathy, in which an amazing prolongation in the survival rate of patients has been achieved over recent decades. A result of this otherwise positive evolution is the fact that bone problems have become a major issue in this group of patients. Through an in-depth review of the related literature, the purpose of this study is to present and comment on the totality of the data that have been published to date pertaining to the prevention and treatment of thalassemia bone-disease, focusing on: the contribution of diet and lifestyle, the treatment of hematologic disease and its complications, the management of hypercalciuria, the role of vitamins and minerals and the implementation of anti-osteoporosis medical regimen. In order to comprehensively gather the above information, we mainly reviewed the international literature through the PubMed database, searching for the preventive and therapeutic data that have been published pertaining to thalassemia bone-disease over the last twenty-nine years. There is no doubt that thalassemia bone-disease is a complication of a multi-factorial etiopathology, which does not follow the rules of classical postmenopausal osteoporosis. Bisphosphonates have been the first line of treatment for many years now, with varied and usually satisfactory results. In addition, over the last few years, more data have arisen for the use of denosumab, teriparatide, and other molecules that are in the clinical trial phase, in beta-thalassemia.

A correction to this paper has been published: https://doi.org/10.1007/s00223-021-00839-y

Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) exhibit osteoporosis and increased fracture risk. Dual-energy X-ray absorptiometry scan measurements and calculation of fracture risk assessment toll score underestimate fracture risk in these patients and do not estimate bone quality. Trabecular bone score (TBS) has been recently proposed as an indirect measure of bone microarchitecture. In this study, we investigated alterations of bone quality in patients with ESRD on HD, using TBS. Fifty patients with ESRD on HD, with a mean age 62 years, and 52 healthy individuals matched for age, body mass index, and gender, were enrolled. All participants had a bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry scan at the lumbar spine, femoral neck, total hip, and 1/3 radius. TBS was evaluated using TBS iNsight. Serum fetuin-A and plasma fibroblast growth factor-23 (FGF-23) (C-terminal) were also measured. Patients on dialysis had significantly lower BMD values at all skeletal sites measured. Plasma FGF-23 levels significantly increased and serum fetuin-Α significantly decreased in patients on dialysis compared with controls. TBS was significantly reduced in patients on dialysis compared with controls (1.11 ± 0.16 vs 1.30 ± 0.13, p

Epidemiological data report that several countries with a high prevalence of hypovitaminosis D may have increased susceptibility to complications and mortality due to COVID-19 infection. These reports, however, have limitations given that they derive from observational studies. Nevertheless, while awaiting more robust data, clinicians should treat patients with vitamin D deficiency irrespective of whether or not it has a link with respiratory infections.

Denosumab (Dmab), a monoclonal antibody against the receptor activator of nuclear factor-κB (RANK) ligand (RANKL) which substantially suppresses osteoclast activity, has been approved for the treatment of common metabolic bone diseases, including postmenopausal osteoporosis, male osteoporosis, and glucocorticoid-induced osteoporosis, in which the pathway of the RANK/RANKL/osteoprotegerin is dysregulated. However, the imbalance of RANKL/RANK/osteoprotegerin is also implicated in the pathogenesis of several other rare metabolic bone diseases, including Juvenile Paget disease, fibrous dysplasia, Hajdu Cheney syndrome and Langerhans cell histiocytosis, thus rendering Dmab a potential treatment option for these diseases. Dmab has been also administered off-label in selected patients (e.g., with Paget's disease, osteogenesis imperfecta, aneurysmal bone cysts) due to contraindications or unresponsiveness to standard treatment, such as bisphosphonates. Moreover, Dmab was administered to improve hypercalcemia induced by various diseases, including primary hyperparathyroidism, tuberculosis and immobilization. The aim of this review is to summarize existing evidence on off-label uses of Dmab in metabolic bone diseases and provide opinion for or against its use, which should be always considered on an individual basis.

We report the updated guidelines for the management of osteoporosis in Greece, which include guidance on fracture risk assessment, diagnosis-pharmacological treatment-follow-up of osteoporosis based on updated information, and national evidence from Greek clinical practice and the healthcare setting. The purpose of this report was to update the Guidelines for the Management of Osteoporosis in Greece that was published in 2011. In line with the GRADE system, the working group initially defined the main clinical questions that should be addressed when dealing with the diagnosis and management of osteoporosis in clinical practice in Greece. Following a literature review and discussion on the experience gained from the implementation of the 2011 Guidelines transmitted through the national electronic prescription network, the Hellenic Society for the Study of Bone Metabolism (HSSBM) uploaded an initial draft for an open dialogue with the relevant registered medical societies and associations on the electronic platform of the Greek Ministry of Health. After revisions, the Central Health Council approved the final document. The 2018 Guidelines provide comprehensive recommendations on the issues of the timing of fracture risk evaluation and dual-energy X-ray absorptiometry (DXA) measurement, interpretation of the DXA results, the diagnostic work-up for osteoporosis, the timing as well as the suggested medications for osteoporosis treatment, and the follow-up methodology employed during osteoporosis treatment. These updated guidelines were designed to offer valid guidance on fracture risk assessment, diagnosis-pharmacological treatment-follow-up of osteoporosis based on updated information and national evidence from clinical practice and the healthcare setting. Clinical judgment is essential in the management of every individual patient for the purpose of achieving the optimal outcome in the safest possible way.

Studies in postmenopausal women have identified sclerostin as a strong candidate for mediating estrogen effects on the skeleton. The effects of estradiol on sclerostin and Dickkopf-1 in younger women remain unclear. The main purpose of this study is to investigate the impact of estradiol and gonadotrophins fluctuations during the menstrual cycle on circulating sclerostin and Dickkopf-1 levels and the possible relationship of sclerostin and Dickkopf-1 with changes in N-terminal propeptide of type 1 collagen and C-telopeptide of collagen cross-links. Fourteen healthy premenopausal Caucasian women, with regular menses, aged 33.6 ± 4.5 years participated. After the first day of menstruation and every-other-day up to the next menses, fasting serum estradiol, luteinizing hormone, follicle-stimulating hormone, sclerostin, Dickkopf-1, N-terminal propeptide of type 1 collagen, and C-telopeptide of collagen cross-links levels were measured in peripheral blood. Participants completed dietary questionnaires and the International physical activity questionnaire during the cycle. Neither sclerostin nor Dickkopf-1 levels changed significantly across the menstrual cycle (p = 0.18 and p = 0.39, respectively), while N-terminal propeptide of type 1 collagen and C-telopeptide of collagen cross-links levels presented cyclic variation (p

Pregnancy-lactation osteoporosis (PLO) is a rare condition with most cases appearing during the third trimester of pregnancy or early in the post-partum period, especially in primigravid women. Our knowledge concerning its pathogenesis is scarce although it seems that most women who experience fragility fractures during this period have a pre-existing bone disease which is further burdened by the mechanical and metabolic changes during pregnancy and lactation. Breastfeeding produces an obligatory loss of maternal skeletal mineral which contributes to the decline of bone density. Little is known whether pharmacological treatments exert a beneficial role upon the situation of PLO since there is lack of firm evidence and bone density seems to recumb spontaneously during weaning.

Osteogenesis imperfecta (OI) is a skeletal dysplasia characterized by brittle bones and extraskeletal manifestations. The disease phenotype varies greatly. Most commonly, OI arises from monoallelic mutations in one of the two genes encoding type I collagen, COL1A1 and COL1A2 and is inherited as an autosomal dominant trait. Here, we describe a consanguineous family with autosomal recessive OI caused by a novel homozygous glycine substitution in COL1A2, NM_000089.3: c.604G > A, p.(Gly202Ser), detected by whole-genome sequencing. The index patient is a 31-year-old Greek woman with severe skeletal fragility. She had mild short stature, low bone mineral density of the lumbar spine and blue sclerae. She had sustained multiple long bone and vertebral fractures since childhood and had been treated with bisphosphonates for several years. She also had an affected sister with similar clinical manifestations. Interestingly, the parents and one sister, all carriers of the COL1A2 glycine mutation, did not have manifestations of OI. In summary, we report on autosomal recessive OI caused by a homozygous glycine-to-serine substitution in COL1A2, leading to severe skeletal fragility. The mutation carriers lacked OI manifestations. This family further expands the complex genetic spectrum of OI and underscores the importance of genetic evaluation for correct genetic counselling.

Summary Tumor-induced osteomalacia (TIO) is a rare form of hypophosphatemia usually caused by phosphaturic mesenchymal tumors (PMTs); the biologic behavior of PMTs is under investigation. Herein we present a case of TIO with a protracted course over 12 years leading to a fatal outcome. A 39-year-old man presented with weakness in 2004 and was found to have decreased serum phosphorus, phosphaturia and low levels of 1,25-dihydroxyvitamin D3. Four years later he developed a painful left calf mass. The lesion was resected, but recurred causing extreme pain and dysfunction. Radiological examination showed a large cluster of soft tissue tumors affecting all the muscle compartments of the calf and a smaller lesion inside the metaphysis of the tibia. Above-knee amputation was performed. Histological examination of all lesions showed a cellular spindle cell neoplasm with variously sized vessels, wide vessel-like spaces and scattered deposits of calcified extracellular material. The tumor infiltrated skeletal muscles, subcutaneous fat and the proximal end of the fibula. The tibial lesion had identical histology. Three years after the amputation the patient presented with cough and dyspnea. Radiological examination, followed by an open biopsy, showed that there were multiple metastatic nodules of PMTs in both lungs. Shortly after the diagnosis the patient died. This case illustrates that even benign cases of PMTs may lead to a fatal outcome and the classification of PMTs into benign and malignant should be reassessed in order to correspond to its biological behavior. Learning points: PMTs, aside from having locally aggressive behavior, may metastasize and cause death PMTs may behave aggressively despite ‘benign’ histological findings Accurate diagnosis of tumor-induced osteomalacia and patient management require a multidisciplinary approach

Vitamin D deficiency and quantitative ultrasound measurements are associated with bone fragility. We assessed these parameters and their correlates. 87.7% of the population has vitamin D inadequacy and this correlated with lifestyle factors. These results contribute to epidemiological data needed for population guidelines for bone health. Vitamin D deficiency and quantitative ultrasound (QUS) parameters are among the most important clinical risk factors of bone fragility. Few data are available for Greek population. The aim of the study was to evaluate the serum 25-hydroxyvitamin D [25(OH)D] level and their determinants, as well as QUS parameters in Greek population. OSTEOS is an observational cross-sectional study conducted from June 2010 to July 2012. Nine hundred seventy adults were recruited from rural and urban areas throughout Greece and completed the appropriate questionnaire. Serum 25(OH)D measured by enzyme immunoassay, QUS parameters, broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI), was assessed with an Achilles device. Univariate Analysis of Variance was used for the assessment of serum 25(OH)D determinants. Mean serum 25(OH)D of the total population was 20,00 ± 8,00 ng/mL. Females had lower levels than males. The negative determinants of serum 25(OH)D in the total population were the female sex and the winter-spring season of sampling while age proved negative association solely in obese subjects. Positive determinants of vitamin D status were summer sun exposure and organized physical activity as expected. Urban had lower SOS and SI than rural residents. Individuals with 25(OH)D ≥ 20 ng/mL had higher SOS than those with 25(OH)D

The introduction into clinical practice of bone turnover markers (BTM) has made possible the noninvasive research of various metabolic bone diseases. BTM are peptides, produced by bone cells (osteoblasts, osteocytes, and osteoclasts) that are released into the circulation during the process of bone modeling and remodeling. For clinical purposes BTM are divided into markers of bone formation and markers of bone resorption. Bone formation markers reflect osteoblast activity and include osteocalcin, bone specific alkaline phosphatase, N-terminal, and C-terminal propeptide of type I procollagen. Bone resorption markers are products of collagen degradation and include pyridinoline and deoxypyridinolin cross-links, C-terminal telopeptide, N-terminal telopeptide, and tartrate resistant acid phosphatase 5b (TRAP-5b), an enzyme secreted by osteoclasts, reflecting both their number and activity. Although BTM are relatively easily measured in urine and blood samples, there are several drawbacks, such as the relative lack of high specificity for bone and for a specific metabolic bone disease, the inability to exclusively reflect bone formation or resorption but rather bone remodeling or a particular bone compartment (e.g., trabecular vs. cortical bone, endosteal vs. periosteal envelop). Recent data indicate that BTM might have a role in the prediction of fracture risk and monitoring treatment. However, more work is needed concerning the standardization of the measurements, their value in predicting fracture risk independent of BMD and monitoring treatment.

BACKGROUND Bone disease is a frequent complication of β-thalassemia major (β-ΤΜ) and its etiology is multifactorial. Marrow expansion, chronic hypoxia, endocrine complications, and iron overload caused chiefly by chronic transfusion treatment are significant factors affecting skeletal health. Bone disease is prevalent even among patients on regular transfusions and adequate iron chelation. The life expectancy of patients with β-thalassemia has increased during the past decade and so, nowadays, patients with thalassemia-associated bone disease (TBD) often require long-term management. There are limited data concerning their pharmacologic treatment. Bisphosphonates represent the most widely studied agents in such patients and there are no published studies about the effects of anabolic treatment. Retreatment with teriparatide has only occasionally been studied in patients with osteoporosis. CASE REPORT We present a male adult patient with β-ΤΜ with a history of low bone mass and multiple vertebral fractures, who required sequential treatment for his longstanding bone disease. He had exhibited considerable, albeit delayed, response to a course of teriparatide treatment for 18 months but subsequently, and while on alendronate, sustained an insufficiency fracture at the left ischiopubic ramus. A second trial of teriparatide treatment resulted in further remarkable increase in total hip and femoral neck bone mineral density. We present the patient's response to sequential treatment during an 8-year follow-up. CONCLUSION Teriparatide could represent an alternative treatment for adults with TBD especially when long-term, sequential treatment is needed. Although there are limited data concerning retreatment, in selected cases, this might be considered.

Osteonecrosis of the jaw (ONJ) is a serious side effect of bisphosphonate use in patients with osteoporosis, Paget's disease, hypercalcemia of malignancy, metastatic bone disease and multiple myeloma, although recently this complication has also been reported in patients under non-bisphosphonate medication, such as denosumab and bevacizumab. The occurrence of ONJ is higher in oncology patients treated with high-dose iv bisphosphonates than in osteoporosis patients treated with oral bisphosphonates. Although multiple hypotheses have been proposed, the exact pathogenic mechanism of ONJ still remains unclear. As treatment protocols based on randomized controlled trials (RCTs) do not exist, we critically reviewed the existing data concerning the management of bisphosphonate-related osteonecrosis of the jaw, including the most recent data for the use of teriparatide and hyperbaric oxygen.

Increased fracture risk, traditionally associated with type 1 diabetes, has lately been of great concern in patients with type 2 diabetes. A variable increase in fracture risk has been reported, ranging from 20% to 3-fold, depending on skeletal site, diabetes duration and study design. Longer disease duration, the presence of diabetic complications, inadequate glycemic control, insulin use and increased risk for falls are all reported to increase fracture risk. Patients with type 2 diabetes display a unique skeletal phenotype with either normal or more frequently increased, bone mineral density and impaired structural and geometric properties. Recently, alterations in bone material properties seem to be the predominant defect leading to increased bone fragility. Accumulation of advanced glycation end-products and changes in collagen cross-linking along with suppression of bone turnover seem to be significant factors impairing bone strength. FRAX score has been reported to underestimate fracture risk and lumbar spine BMD is inadequate in predicting vertebral fractures. Anti-diabetic medications, apart from thiazolidinediones, appear to be safe for the skeleton, although more data are needed. Optimal strategies to reduce skeletal fragility in type 2 diabetic patients are yet to be determined.

The interaction between obesity and bone metabolism is complex. The effects of fat on the skeleton are mediated by both mechanical and biochemical factors. Though obesity is characterized by higher bone mineral density, studies conducted on bone microarchitecture have produced conflicting results. The majority of studies indicate that obesity has a positive effect on skeletal strength, even though most likely the effects are site-dependent and, in fact, obese individuals might be at risk of certain types of fractures. Mechanical loading and higher lean mass are associated with improved outcomes, whereas systemic inflammation, observed especially with abdominal obesity, may exert negative effects. Weight loss interventions likely lead to bone loss over time. Pharmacological treatment options seem to be safe in terms of skeletal health; however, the skeletal effects of bariatric surgery are dependent on the type of surgical procedure. Malabsorptive procedures are associated with higher short-term adverse effects on bone health. In this narrative review, we discuss the effects of obesity and weight loss interventions on skeletal health.

Context Expression of microRNAs (miRs) related to bone metabolism in the serum may be affected by antiosteoporotic treatment. Objective To investigate the effect of two antiosteoporotic agents with opposite effects on bone metabolism on miR expression profile in the serum. Design Observational, open label, nonrandomized clinical trial. Setting The outpatient clinics for Metabolic Bone Diseases of 424 General Military Hospital, Thessaloniki, Greece. Patients and interventions Postmenopausal women with low bone mass were treated with either teriparatide (TPTD; n = 30) or denosumab (n = 30) for 12 months. Main outcome measures Changes in the serum expression of selected miRs linked to bone metabolism at 3 and 12 months of treatment. Secondary measurements: associations of measured miRs with changes in bone mineral density (BMD) at 12 months and the bone turnover markers (BTMs) C-terminal cross-linking telopeptide of type I collagen and procollagen type I N-terminal propeptide at 3 and 12 months. Results We found significantly decreased relative expression of miR-33-3p at 3 months (P = 0.03) and of miR-133a at 12 months (P = 0.042) of TPTD treatment. BMD values at 12 months of TPTD treatment were significantly and inversely correlated with miR-124-3p expression at 3 months (P = 0.008). Relative expression of miR-24-3p and miR-27a was correlated with changes in BTMs during TPTD treatment and of miR-21-5p, miR-23a-3p, miR-26a-5p, miR-27a, miR-222-5p, and miR-335-5p with changes in BTMs during denosumab treatment. Conclusions Circulating miRs are differentially affected by treatment with TPTD and denosumab. TPTD affects the relative expression of miRs related to the expression of RUNX-2 (miR-33) and DKK-1 gene (miR-133).

Osteogenesis imperfecta (OI) is the most common inherited form of bone fragility and includes a heterogenous group of genetic disorders which most commonly result from defects associated with type 1 collagen. 85%-90% of cases are inherited in an autosomal dominant manner and are caused by mutations in the COL1A1 and COL1A2 genes, leading to quantitative or qualitative defects in type 1 collagen. In the last decade, defects in several other proteins involved in the normal processing of type 1 collagen have been described. Recent advances in genetics have called for reconsideration of the classification of OI, however, most recent classifications align with the classic clinical classification by Sillence. The hallmark of the disease is bone fragility but other tissues are also affected. Intravenous bisphosphonates (BPs) are the most widely used intervention, having significant favorable effects regarding areal bone mineral density (BMD) and vertebral reshaping following fractures in growing children. BPs have a modest effect in long bone fracture incidence, their effects in adults with OI concerns only BMD, while there are reports of subtrochanteric fractures resembling atypical femoral fractures. Other therapies showing promising results include denosumab, teriparatide, sclerostin inhibition, combination therapy with antiresorptive and anabolic drugs and TGF-β inhibition. Gene targeting approaches are under evaluation. More research is needed to delineate the best therapeutic approach in this heterogeneous disease.

Polyostotic fibrous dysplasia in combination with cafeau-lait macules and hyperfunctioning endocrinopathies consists of a rare clinical condition termed as McCune-Albright syndrome. Aneurysmal bone cysts are tumor-like cystic lesions, composed of blood-filled compartments. They may occur as primary lesions or secondary to other pathologies; most commonly giant cell tumors of bone. However, secondary aneurysmal bone cysts in McCune-Albright syndrome are exceptional. We present a 28-year-old female with McCune-Albright syndrome. She experienced precocious puberty at age 3 months. In childhood, she experienced multiple long bone fractures, facial deformity and progressive visual and hearing impairment. One year ago, she experienced a painful, gradually enlarging bone lesion involving the right ilium, pubic and ischial bone with groundglass appearance, septa, marginal sclerosis, endosteal scalloping and blow-out expansion resulting in localized thinning of the cortex. CT-guided needle biopsy of the pelvic lesion showed aneurysmal bone cyst. Selective arterial embolization was recommended, however, the patient and her relatives did not consent to proceed to treatment, and she remained in close surveillance thereafter.