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Glucocorticoids are effective immunomodulatory drugs used for many inflammatory disorders as well as in transplant recipients. However, both iatrogenic and endogenous glucocorticoid excess are also associated with several side effects including an increased risk of osteoporosis and fractures. Glucocorticoid-induced osteoporosis (GIOP) is a common secondary cause of osteoporosis in adults. Despite availability of clear evidence and international guidelines for the prevention of GIOP, a large treatment gap remains. In this narrative review, the Belgian Bone Club (BBC) updates its 2006 consensus recommendations for the prevention and treatment of GIOP in adults. The pathophysiology of GIOP is multifactorial. The BBC strongly advises non-pharmacological measures including physical exercise, smoking cessation and avoidance of alcohol abuse in all adults at risk for osteoporosis. Glucocorticoids are associated with impaired intestinal calcium absorption; the BBC therefore strongly recommend sufficient calcium intake and avoidance of vitamin D deficiency. We recommend assessment of fracture risk, taking age, sex, menopausal status, prior fractures, glucocorticoid dose, other clinical risk factors and bone mineral density into account. Placebo-controlled randomized controlled trials have demonstrated the efficacy of alendronate, risedronate, zoledronate, denosumab and teriparatide in GIOP. We suggest monitoring by dual-energy X-ray absorptiometry (DXA) and vertebral fracture identification one year after glucocorticoid initiation. The trabecular bone score might be considered during DXA monitoring. Extended femur scans might be considered at the time of DXA imaging in glucocorticoid users on long-term (≥ 3 years) antiresorptive therapy. Bone turnover markers may be considered for monitoring treatment with anti-resorptive or osteoanabolic drugs in GIOP. Although the pathophysiology of solid organ and hematopoietic stem cell transplantation-induced osteoporosis extends beyond GIOP alone, the BBC recommends similar evaluation, prevention, treatment and follow-up principles in these patients. Efforts to close the treatment gap in GIOP and implement available effective fracture prevention strategies into clinical practice in primary, secondary and tertiary care are urgently needed., Competing Interests: ML has received consultancy and lecture fees from Alexion, Amgen, Daiichi Sankyo, Kyowa Kirin, Menarini, Orifarm, Sandoz, Takeda, UCB, and Will Pharma. SG has received consultancy, lecture and travel fees from Alexion, Amgen, MSD, Novartis, Takeda, UCB, and Will Pharma. CV has received travel fees from Boehringer Ingelheim. JB has received consultancy, lecture fees and travel support from Alexion, Amgen, Bayer, Sandoz, Takeda, UCB and Will-Pharma. OB has received consultancy fees from Amgen, Biophytis, IBSA, MEDA, Servier, SMB, Teva, TRB Chemedica, and UCB. EC has received consultancy fees from bioMérieux, DiaSorin, Fujirebio, IDS, Menarini, and Nittobo. SR has received travel and consultancy fees from Abbott, Bayer, Eurogenerics, Gedeon Richter, Mylan, Takeda, Theramex, UCB and Will-Pharma. EG has received travel and consultancy fees from Amgen, Alexion, Daiichi Sankyo, Sandoz, Takeda, UCB, and Will Pharma. The remaining 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 © 2022 Laurent, Goemaere, Verroken, Bergmann, Body, Bruyère, Cavalier, Rozenberg, Lapauw and Gielen.)

Romosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analyzed the data from a study collecting lumbar computed tomography (CT) spine scans at enrollment and 12 months post-treatment with romosozumab (210 mg sc monthly, n = 17), open-label daily teriparatide (20 μg sc, n = 19), or placebo (sc monthly, n = 20). For each of the 56 women, cortical thickness (Ct.Th), endocortical thickness (Ec.Th), cortical bone mineral density (Ct.bone mineral density (BMD)), cancellous BMD (Cn.BMD), and cortical mass surface density (CMSD) were measured across the first lumbar vertebral surface. In addition, color maps of the changes in the lumbar vertebrae structure were statistically analyzed and then visualized on the bone surface. At 12 months, romosozumab improved all parameters significantly over placebo and resulted in a mean vertebral Ct.Th increase of 10.3% versus 4.3% for teriparatide, an Ec.Th increase of 137.6% versus 47.5% for teriparatide, a Ct.BMD increase of 2.1% versus a -0.1% decrease for teriparatide, and a CMSD increase of 12.4% versus 3.8% for teriparatide. For all these measurements, the differences between romosozumab and teriparatide were statistically significant (p < 0.05). There was no significant difference between the romosozumab-associated Cn.BMD gains of 22.2% versus 18.1% for teriparatide, but both were significantly greater compared with the change in the placebo group (-4.6%, p < 0.05). Cortical maps showed the topographical locations of the increase in bone in fracture-prone areas of the vertebral shell, walls, and endplates. This study confirms widespread vertebral bone accrual with romosozumab or teriparatide treatment and provides new insights into how the rapid prevention of vertebral fractures is achieved in women with osteoporosis using these anabolic agents. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Purpose: To provide updated evidence-based guidelines for the management of osteoporosis in postmenopausal women in Belgium., Methods: The Belgian Bone Club (BBC) gathered a guideline developer group. Nine "Population, Intervention, Comparator, Outcome" (PICO) questions covering screening, diagnosis, non-pharmacological and pharmacological treatments, and monitoring were formulated. A systematic search of MEDLINE, the Cochrane Database of Systematic Reviews, and Scopus was performed to find network meta-analyses, meta-analyses, systematic reviews, guidelines, and recommendations from scientific societies published in the last 10 years. Manual searches were also performed. Summaries of evidence were provided, and recommendations were further validated by the BBC board members and other national scientific societies' experts., Results: Of the 3840 references in the search, 333 full texts were assessed for eligibility, and 129 met the inclusion criteria. Osteoporosis screening using clinical risk factors should be considered. Patients with a recent (<2 years) major osteoporotic fracture were considered at very high and imminent risk of future fracture. The combination of bone mineral density measured by dual-energy X-ray absorptiometry and 10-year fracture risk was used to categorize patients as low or high risk. Patient education, the combination of weight-bearing and resistance training, and optimal calcium intake and vitamin D status were recommended. Antiresorptive and anabolic osteoporosis treatment should be considered for patients at high and very high fracture risk, respectively. Follow-up should focus on compliance, and patient-tailored monitoring should be considered., Conclusion: BBC guidelines and 25 guideline recommendations bridge the gap between research and clinical practice for the screening, diagnosis, and management of osteoporosis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This narrative review discusses several aspects of the management of osteoporosis in patients under 50 years of age. Peak bone mass is genetically determined but can also be affected by lifestyle factors. Puberty constitutes a vulnerable period. Idiopathic osteoporosis is a rare, heterogeneous condition in young adults due in part to decreased osteoblast function and deficient bone acquisition. There are no evidence-based treatment recommendations. Drugs use can be proposed to elderly patients at very high risk. Diagnosis and management of osteoporosis in the young can be challenging, in particular in the absence of a manifest secondary cause. Young adults with low bone mineral density (BMD) do not necessarily have osteoporosis and it is important to avoid unnecessary treatment. A determination of BMD is recommended for premenopausal women who have had a fragility fracture or who have secondary causes of osteoporosis: secondary causes of excessive bone loss need to be excluded and treatment should be targeted. Adequate calcium, vitamin D, and a healthy lifestyle should be recommended. In the absence of fractures, conservative management is generally sufficient, but in rare cases, such as chemotherapy-induced osteoporosis, antiresorptive medication can be used. Osteoporosis in young men is most often of secondary origin and hypogonadism is a major cause; testosterone replacement therapy will improve BMD in these patients. Diabetes is characterized by major alterations in bone quality, implying that medical therapy should be started sooner than for other causes of osteoporosis. Primary hyperparathyroidism, hyperthyroidism, Cushing's syndrome and growth hormone deficiency or excess affect cortical bone more often than trabecular bone., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Osteoporosis causes high individual and societal burden, due to limited attention to fracture prevention. Integrated care for chronic conditions has shown to facilitate management of these conditions, improving clinical outcomes alongside quality of life and cost-effectiveness. This manuscript describes an integrated osteoporosis care programme that will be implemented in primary care., Objective: To provide a comprehensive description of a quasi-experimental study design in which a newly developed integrated osteoporosis care (IOC) programme for the management of postmenopausal osteoporosis (PO) in primary care (PC) is implemented and will be compared with care as usual (CAU)., Methods: A literature research was performed and expert meetings have been taking place, which has led to the development of a complex PC intervention based on framework for integrated people-centred health services (IPCHS)., Results: This manuscript describes the developmental process of the preclinical phase of a quasi-experimental real-world design and the interventions as a result of this process that will be implemented during the clinical phase, along with the evaluation that will take place alongside the clinical phase: An integrative approach for the management of PO in primary care was developed and will be implemented in greater region of Ghent (GRG), Belgium. The approach consists of a complex intervention targeting patients and PC stakeholders in osteoporosis care (e.g. general practitioners (GPs), physiotherapists, nurses, pharmacists). A comparison will be made with CAU using medication possession ratios (MPR) of included patients as primary outcome. These data will be obtained from the national health database. Secondary outcomes are physician outcomes, patient-reported outcome measures (PROMs), and patient-reported experience measures (PREMs). A cost-effectiveness evaluation will be performed if the programme appears to be effective in terms of MPR., Trial Registration: ClinicalTrials.gov : NCT03970902.

Context: Globally, one in five men aged >50 years is predicted to experience an osteoporotic fracture. Because of the treatment gap in osteoporosis and the paucity of bone-forming agents for men, new osteoporosis treatments are needed., Objective: To evaluate the safety and efficacy of romosozumab in men with osteoporosis., Design: Phase III randomized BRIDGE study (placebo-controlled double-blind study evaluating the efficacy and safety of romosozumab in treating men with osteoporosis; ClinicalTrials.gov identifier, NCT02186171) for 12 months., Setting: Thirty-one centers in Europe, Latin America, Japan, and North America., Patients: Men aged 55 to 90 years with a baseline bone mineral density (BMD) T-score at the lumbar spine (LS), total hip (TH), or femoral neck of ≤-2.5 or ≤-1.5 with a history of a fragility nonvertebral or vertebral fracture., Interventions: The subjects were randomized 2:1 to receive romosozumab 210 mg subcutaneously monthly or placebo for 12 months., Main Outcome Measures: The primary efficacy endpoint was percentage change from baseline in LS BMD at month 12., Results: In 245 subjects (163 romosozumab, 82 placebo), at month 12, the mean percentage change from baseline in the LS and TH BMD was significantly greater for the romosozumab group than for the placebo group (LS, 12.1% vs 1.2%; TH, 2.5% vs -0.5%; P < 0.001). Adverse events and serious adverse events were balanced between the two groups, with a numerical imbalance in the positively adjudicated cardiovascular serious adverse events [romosozumab, 8 (4.9%) vs placebo, 2 (2.5%)]., Conclusions: Treatment with romosozumab for 12 months increased the spine and hip BMD compared with placebo and was well tolerated in men with osteoporosis.

In this consensus paper, the Belgian Bone Club aims to provide a state of the art on the epidemiology, diagnosis, and management of osteoporosis in frail individuals, including patients with anorexia nervosa, patients on dialysis, cancer patients, persons with sarcopenia, and the oldest old. All these conditions may indeed induce bone loss that is superimposed on physiological bone loss and often remains under-recognized and under-treated. This is of particular concern because of the major burden of osteoporotic fractures in terms of morbidity, mortality, and economic cost. Therefore, there is an urgent need to appreciate bone loss associated with these conditions, as this may improve diagnosis and management of bone loss and fracture risk in clinical practice.

Context: The increased fracture risk associated with type 1 diabetes mellitus (T1DM) remains unexplained by traditional risk factors such as low areal bone mineral density (aBMD). Nonetheless, few data exist on other determinants of bone strength in T1DM, including volumetric bone mineral density (vBMD) and bone geometry., Objective: We compared areal and volumetric bone parameters and cortical bone geometry in adult T1DM patients and sex- and age-matched controls., Design: Cross-sectional study including 64 adult T1DM patients (38 men; mean age, 41.1 ± 8.1 years) and 63 sex- and age-matched controls., Main Outcome Measures: Areal bone parameters using dual-energy X-ray absorptiometry; volumetric bone parameters and cortical bone geometry using peripheral quantitative computed tomography., Results: T1DM was associated with lower aBMD at the total body, femoral neck, and total hip; lower trabecular vBMD at the distal radius; and higher cortical but lower total vBMD at the radial shaft. In addition, subjects with T1DM had a similar periosteal but larger endosteal circumference, smaller cortical thickness, and lower cortical over total bone area ratio. Differences in bone parameters could not be explained by differences in bone turnover markers or body composition, but cortical area was inversely associated with glycemic variability and long-term glycemic control., Conclusions: Besides decreased aBMD and trabecular vBMD, adult T1DM patients present with a cortical bone size deficit, which may contribute to their increased fracture risk. This deficit is mainly situated at the endosteal envelope, suggesting imbalanced remodeling rather than compromised modeling processes as the underlying mechanism., (Copyright © 2017 Endocrine Society)

Objectives: To estimate the preferences of osteoporotic patients for medication attributes, and analyse data from seven European countries., Methods: A discrete choice experiment was conducted in Belgium, France, Ireland, the Netherlands, Spain, Switzerland and the UK. Patients were asked to choose repeatedly between two hypothetical unlabelled drug treatments (and an opt-out option) that varied with respect to four attributes: efficacy in reducing the risk of fracture, type of potential common side effects, and mode and frequency of administration. In those countries in which patients contribute to the cost of their treatment directly, a fifth attribute was added: out-of-pocket cost. A mixed logit panel model was used to estimate patients' preferences., Results: In total, 1124 patients completed the experiment, with a sample of between 98 and 257 patients per country. In all countries, patients preferred treatment with higher effectiveness, and 6-monthly subcutaneous injection was always preferred over weekly oral tablets. In five countries, patients also preferred a monthly oral tablet and yearly i.v. injections over weekly oral tablets. In the three countries where the out-of-pocket cost was included as an attribute, lower costs significantly contributed to the treatment preference. Between countries, there were statistically significant differences for 13 out of 42 attribute/level interactions., Conclusion: We found statistically significant differences in patients' preferences for anti-osteoporosis medications between countries, especially for the mode of administration. Our findings emphasized that international treatment recommendations should allow for local adaptation, and that understanding individual preferences is important if we want to improve the quality of clinical care for patients with osteoporosis., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

The exact role of biochemical markers of bone turnover in the management of metabolic bone diseases remains a topic of controversy. In this consensus paper, the Belgian Bone Club aimed to provide a state of the art on the use of these biomarkers in different clinical or physiological situations like in postmenopausal women, osteoporosis in men, in elderly patients, in patients suffering from bone metastasis, in patients with chronic renal failure, in pregnant or lactating women, in intensive care patients, and in diabetics. We also gave our considerations on the analytical issues linked to the use of these biomarkers, on potential new emerging biomarkers, and on the use of bone turnover biomarkers in the follow-up of patients treated with new drugs for osteoporosis.

One in three osteoporotic fractures occur in men and the consequences of a fracture in men tend to be more severe than in women. Still, only a small minority of men with high risk of fracture are detected and treated. Although there are gender differences in the pathophysiology of osteoporosis, such as in the pattern of bone loss, similarities predominate, which is also the case for clinical risk factors. It seems appropriate to consider treatment for men and women with a similar 10 year fracture risk. Drugs now approved for treatment of osteoporosis in men include the anti-resorptive bisphosphonates alendronate, residronate and zoledronic acid, the anti-resorptive drug denosumab, the bone-forming agent teriparatide, and (not in the US) strontium ranelate with mild opposite effects on resorption and formation. Although the evidence level for efficacy and safety of these drugs in men is still relatively limited, available data indicate that treatment effects in men are very similar to what has been observed in the treatment of postmenopausal osteoporosis. Denosumab is also approved for treatment in men receiving androgen deprivation therapy for non-metastatic prostate cancer; bisphosphonates and teriparatide are also available to clinicians for treatment of glucocorticoid-induced osteoporosis in men. Testosterone treatment may be indicated in men with documented symptomatic hypogonadism, but osteoporosis is neither a sufficient nor a specific indication for testosterone treatment. New compounds with well advanced clinical development include odanacatib, a selective inhibitor of the cysteine protease cathepsin-K, and romosozumab, a monoclonal antibody against sclerostin., (Copyright © 2014. Published by Elsevier Ltd.)

Introduction: The patient's perspective is becoming increasingly important in clinical and policy decisions. In this study, we aimed to evaluate the preferences of patients with, or at risk of, osteoporosis for medication attributes, and to establish how patients trade between these attributes., Methods: A discrete choice experiment survey was designed and patients were asked to choose between two hypothetical unlabelled drug treatments (and an opt-out option) that vary in five attributes: efficacy in reducing the risk of fracture, type of potential common side-effects, mode and frequency of administration and out-of-pocket costs. An efficient experimental design was used to construct the treatment option choice sets and a mixed logit panel data model was used to estimate patients' preferences and trade-offs between attributes., Results: A total of 257 patients with, or at risk of, osteoporosis completed the experiment. As expected, patients preferred treatment with higher effectiveness and lower cost. They also preferred either an oral monthly tablet or 6-month subcutaneous injection above weekly oral tablets, 3-month subcutaneous, 3-month intravenous or yearly intravenous injections. Patients disliked being at risk of gastro-intestinal disorders more than being at risk of skin reactions and flu-like symptoms. There was significant variation in preferences across the sample for all attributes except subcutaneous injection., Conclusions: This study revealed that osteoporotic patients preferred 6-month subcutaneous injection and oral monthly tablet, and disliked gastro-intestinal disorders. Moreover, patients were willing to pay a personal contribution or to trade treatment efficacy for better levels of other attributes. Preferences for treatment attributes varied across patients and this highlights the importance of clinical decision-making taking individual preferences into account to improve osteoporosis care.

We review the various aspects of health technology assessment in osteoporosis, including epidemiology and burden of disease, and assessment of the cost-effectiveness of recent advances in the treatment of osteoporosis and the prevention of fracture, in the context of the allocation of health-care resources by decision makers in osteoporosis. This article was prepared on the basis of a symposium held by the Belgian Bone Club and the discussions surrounding that meeting and is based on a review and critical appraisal of the literature. Epidemiological studies confirm the immense burden of osteoporotic fractures for patients and society, with lifetime risks of any fracture of the hip, spine, and forearm of around 40 % for women and 13 % for men. The economic impact is also large; for example, Europe's six largest countries spent €31 billion on osteoporotic fractures in 2010. Moreover, the burden is expected to increase in the future with demographic changes and increasing life expectancy. Recent advances in the management of osteoporosis include novel treatments, better fracture-risk assessment notably via fracture risk algorithms, and improved adherence to medication. Economic evaluation can inform decision makers in health care on the cost-effectiveness of the various interventions. Cost-effectiveness analyses suggest that the recent advances in the prevention and treatment of osteoporosis may constitute an efficient basis for the allocation of scarce health-care resources. In summary, health technology assessment is increasingly used in the field of osteoporosis and could be very useful to help decision makers efficiently allocate health-care resources.

Objective: Long-term glucocorticoid use is accompanied by rapid bone loss; however, early treatment with bisphosphonates prevents bone loss and reduces fracture risk. The aim of this study was to examine the effects of two bisphosphonates, i.v. zoledronic acid (ZOL) versus oral risedronate (RIS), on bone turnover markers (BTMs) in subjects with glucocorticoid-induced osteoporosis (GIO)., Methods: Patients were randomly stratified according to the duration of pre-study glucocorticoid therapy [prevention subpopulation (ZOL, n = 144; RIS, n = 144) ≤3 months, treatment subpopulation (ZOL, n = 272; RIS, n = 273) >3 months]. Changes in β-C-terminal telopeptides of type 1 collagen (β-CTx), N-terminal telopeptide of type I collagen (NTx), procollagen type 1 N-terminal propeptide (P1NP) and bone-specific alkaline phosphatase (BSAP) from baseline were measured on day 10 and months 3, 6 and 12., Results: At most time points, there were significantly greater reductions (P < 0.05) in the concentrations of serum β-CTx, P1NP and BSAP and urine NTx in subjects on ZOL compared with RIS in both males and females of the treatment and prevention subpopulations. In pre- and post-menopausal women, there were significantly greater reductions in the concentrations of BTMs with ZOL compared with RIS. At 12 months, ZOL had significantly greater reductions compared with RIS (P < 0.05) for β-CTx, P1NP, BSAP and NTx levels, independent of glucocorticoid dose., Conclusions: Once-yearly i.v. infusion of ZOL 5 mg was well tolerated in different subgroups of GIO patients. ZOL was non-inferior to RIS and even superior to RIS in the response of BTMs in GIO patients., Trial Registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT00100620.

Objective: Sclerostin inhibits osteoblast differentiation and bone formation. If aberrant sclerostin action is involved in less efficient bone acquisition in men with idiopathic low bone mass, this might be reflected in higher serum sclerostin levels., Methods: In 116 men with idiopathic osteoporosis (≤65 years old), 40 of their sons and healthy controls, areal bone parameters were measured using dual-energy X-ray absorptiometry, and volumetric and geometric bone parameters were measured using peripheral quantitative computed tomography. Serum analytes were measured using immunoassays and estradiol (E2) levels using liquid chromatography-tandem mass spectrometry., Results: Men with idiopathic low bone mass had lower levels of sclerostin than the controls (0.54±0.17 vs 0.66±0.23 ng/ml; P<0.001). In both groups, sclerostin levels were strongly associated with age; when adjusting for age, no associations with anthropometrics were observed (P>0.14). In multivariate analyses, sclerostin levels displayed a positive association with whole-body bone mineral content (BMC) and areal BMD (aBMD), as well as with trabecular and cortical volumetric bone mineral density (vBMD) at the tibia in the probands. No clear associations were observed in the control group, neither were sclerostin levels associated with BMC at the radius or lumbar spine (all P>0.11). Testosterone, but not E2, was inversely related to sclerostin levels in the probands. No difference in sclerostin levels was found in their sons when compared with their controls., Conclusion: Lower rather than higher serum sclerostin levels in the probands with idiopathic low bone mass suggest that aberrant sclerostin secretion is not involved in the pathogenesis of low bone mass in these subjects.

Context: Strontium ranelate reduces vertebral and nonvertebral fracture risk in postmenopausal osteoporosis., Objective: The objective of this study was to determine the efficacy and safety of strontium ranelate in osteoporosis in men over 2 years (main analysis after 1 year)., Design: This was an international, unbalanced (2:1), double-blind, randomized placebo-controlled trial (MALEO [MALE Osteoporosis])., Setting: This international study included 54 centers in 14 countries., Participants: PARTICIPANTS were 261 white men with primary osteoporosis., Intervention: Strontium ranelate at 2 g/d (n = 174) or placebo (n = 87) was administered., Main Outcome Measures: Lumbar spine (L2-L4), femoral neck, and total hip bone mineral density (BMD), biochemical bone markers, and safety were measured., Results: Baseline characteristics were similar in both groups in the whole population (age, 72.9 ± 6.0 years; lumbar spine BMD T-score, -2.7 ± 1.0; femoral neck BMD T-score, -2.3 ± 0.7). Men who received strontium ranelate over 2 years had greater increases in lumbar spine BMD than those who received placebo (relative change from baseline to end, 9.7% ± 7.5% vs 2.0% ± 5.5%; between-group difference estimate (SE), 7.7% (0.9%); 95% confidence interval, 5.9%-9.5%; P < .001). There were also significant between-group differences in relative changes in femoral neck BMD (P < .001) and total hip BMD (P < .001). At the end of treatment, mean levels of serum cross-linked telopeptides of type I collagen, a marker of bone resorption, were increased in both the strontium ranelate group (10.7% ± 58.0%; P = .022) and the placebo group (34.9% ± 65.8%; P < .001). The corresponding mean changes of bone alkaline phosphatase, a marker of bone formation, were 6.4% ± 28.5% (P = .005) and 1.9% ± 25.4% (P = .505), respectively. After 2 years, the blood strontium level (129 ± 66 μmol/L) was similar to that in trials of postmenopausal osteoporosis. Strontium ranelate was generally well tolerated., Conclusions: The effects of strontium ranelate on BMD in osteoporotic men were similar to those in postmenopausal osteoporotic women, supporting its use in the treatment of osteoporosis in men.

Unlabelled: Drugs used for the prevention and the treatment of osteoporosis exert various favourable and unfavourable extra-skeletal effects whose importance is increasingly recognized notably for treatment selection., Introduction: The therapeutic armamentarium for the prevention and the treatment of osteoporosis is increasingly large, and possible extra-skeletal effects of available drugs could influence the choice of a particular compound., Methods: The present document is the result of a national consensus, based on a systematic and critical review of the literature., Results: Observational research has suggested an inverse relationship between calcium intake and cardiovascular diseases, notably through an effect on blood pressure, but recent data suggest a possible deleterious effect of calcium supplements on cardiovascular risk. Many diverse studies have implicated vitamin D in the pathogenesis of clinically important non-skeletal functions or diseases, especially muscle function, cardiovascular disease, autoimmune diseases and common cancers. The possible effects of oral or intravenous bisphosphonates are well-known. They have been associated with an increased risk of oesophageal cancer or atrial fibrillation, but large-scale studies have not found any association with bisphosphonate use. Selective oestrogen receptor modulators have demonstrated favourable or unfavourable extra-skeletal effects that vary between compounds. Strontium ranelate has a limited number of non-skeletal effects. A reported increase in the risk of venous thromboembolism is not found in observational studies, and very rare cases of cutaneous hypersensitivity reactions have been reported. Denosumab has been introduced recently, and its extra-skeletal effects still have to be assessed., Conclusion: Several non-skeletal effects of bone drugs are well demonstrated and influence treatment choices.

This consensus article reviews the various aspects of the non-pharmacological management of osteoporosis, including the effects of nutriments, physical exercise, lifestyle, fall prevention, and hip protectors. Vertebroplasty is also briefly reviewed. Non-pharmacological management of osteoporosis is a broad concept. It must be viewed as an essential part of the prevention of fractures from childhood through adulthood and the old age. The topic also includes surgical procedures for the treatment of peripheral and vertebral fractures and the post-fracture rehabilitation. The present document is the result of a consensus, based on a systematic review and a critical appraisal of the literature. Diets deficient in calcium, proteins or vitamin D impair skeletal integrity. The effect of other nutriments is less clear, although an excessive consumption of sodium, caffeine, or fibres exerts negative effects on calcium balance. The deleterious effects of tobacco, excessive alcohol consumption and a low BMI are well accepted. Physical activity is of primary importance to reach optimal peak bone mass but, if numerous studies have shown the beneficial effects of various types of exercise on bone mass, fracture data as an endpoint are scanty. Fall prevention strategies are especially efficient in the community setting, but less evidence is available about their effectiveness in preventing fall-related injuries and fractures. The efficacy of hip protectors remains controversial. This is also true for vertebroplasty and kyphoplasty. Several randomized controlled studies had reported a short-term advantage of vertebroplasty over medical treatment for pain relief, but these findings have been questioned by recent sham-controlled randomized clinical studies.

Context: Pathophysiology of deficient bone mass acquisition in male idiopathic osteoporosis (IO) remains poorly understood., Objective: Our objective was to investigate volumetric and geometric parameters of the appendicular skeleton, biochemical markers, and anthropometrics in men with IO., Design, Setting, and Participants: Our cross-sectional study included 107 men diagnosed with idiopathic low bone mass, 23 of their adult sons, and 130 age-matched controls., Main Outcome Measures: Body composition and areal bone parameters (dual-energy x-ray absorptiometry) and volumetric and geometric parameters of radius and tibia (peripheral quantitative computed tomography) were assessed. Serum levels of testosterone, estradiol (E(2)), and SHBG, and bone turnover markers were measured using immunoassays. Free hormone fractions were calculated., Results: Men with idiopathic low bone mass had lower weight (-9.6%), truncal height (-3.3%), and upper/lower body segment ratio (-2.7%; all P < 0.001) and presented at the radius and tibia lower trabecular (-19.0 and -23.6%, respectively; both P < 0.001) and cortical volumetric bone mineral density (vBMD) (-2.4 and -1.7%; both P < 0.001) and smaller cortical areas (-9.7 and -13.6%; both P < 0.001) and thicknesses (-13.5 and -14.5%, both P < 0.001) due to larger endosteal circumferences (+11.8 and +7.4%, both P < 0.001) than controls. Furthermore, (free) E(2) was lower and SHBG higher (both P < 0.01). Their sons had lower trabecular vBMD (-10.3%, P = 0.036) and a thinner cortex (-8.3%, P = 0.024) at the radius., Conclusion: Bone mass deficits in men with idiopathic low bone mass involve trabecular and cortical bone, resulting from lower vBMD and smaller cortical bone cross-sectional areas and thicknesses. A similar bone phenotype is present in at least part of their sons. The lower E(2), together with characteristics as lower upper/lower body segment ratio, larger endosteal circumferences and lower vBMD, may indicate an estrogen-related factor in the pathogenesis of male IO.

Bone health is a parameter of interest in the daily follow-up of male-to-female (M --> F) transsexual persons both before and after sex reassignment surgery (SRS) due to an intensely changing hormonal milieu. We have studied body composition, areal, geometric, and volumetric bone parameters, using DXA and peripheral quantitative computed tomography at different sites in 50 M --> F transsexual persons, at least 3 yr after the start of the hormonal treatment and 1 yr after SRS. In this cross-sectional study, hormone levels and markers of bone metabolism were assessed using immunoassays. Prevalence of low bone mass as defined by a Z-score < or = -2.0 according to DXA criteria was 26% at lumbar spine and 2% at the total hip. We found no major differences in hormonal parameters between participants with a Z-score < or = or > -2.0. Markers of bone turnover were comparable between subjects with or without low bone mass, indicating a stable bone turnover at the time of investigation. No significant differences in bone size or density were observed between patients on transdermal vs. oral estrogens. Low bone mass is not uncommon in M --> F transsexual persons. Smaller bone size, and a strikingly lower muscle mass compared with men appear to underlie these findings.

About one in three osteoporotic fractures occur in men, and the consequences of fractures are more severe in men. However, only too few men at high risk of fracture are detected and treated. There is no consensus definition of osteoporosis in men based on bone mineral density (BMD), and therapeutic decisions should be based on absolute fracture risk as estimated from age, BMD, fracture history, and additional clinical risk factors. In men, secondary osteoporosis deserves particular attention. Genetically determined alterations of bone mass acquisition during growth are involved in idiopathic osteoporosis in the young, whereas senile osteoporosis involves progressive bone loss throughout adult life. Estradiol appears to be the predominant sex steroid involved in regulation of bone maturation and metabolism. The evidence base for the long-term efficacy and safety of therapies for osteoporosis in men, including the bone-active agents (i.e. bisphosphonates and teriparatide), is limited, so that they should be applied with discernment based on clinical judgement and careful estimation of fracture risk.

Osteoporotic fractures are an increasing cause of mortality and morbidity in ageing populations. A major risk determinant for these fractures is bone mineral density (BMD). Variation on BMD is thought, on the basis of twin and family studies, to be subject to a large amount of genetic variation and it has been hypothesised that this may be due to the influence of multiple genes. However, in families showing segregation of low or high BMD, single major genes have been shown to play a crucial role. We performed a genome-wide screen using 380 microsatellite markers in a single extended family (n=34) in which early-onset low spinal areal BMD segregates in an autosomal dominant-like fashion. A two-point linkage analysis was performed, revealing a maximum LOD score of 3.07 on 1p36.3 (D1S468), confirming results of previous linkage studies of BMD, while no other suggestive linkage peaks (LOD>2.2) were detected elsewhere in the genome. Microsatellite markers were subsequently genotyped for a +/-6.9 Mb region surrounding D1S468. This revealed critical recombination events restricting the candidate region to 1.2 Mb and 19 genes. Sequencing analysis of the coding region of candidate genes WDR8 and EGFL3 revealed no mutations or disease-associated polymorphisms. Our results provide some evidence supporting the hypothesis that there are genetic determinants for spinal BMD on 1p36.3. Although no specific disease causing mutation has yet been found, the delineation of a relatively small candidate region in a single extended family opens perspectives to identify a major gene for spinal BMD.

Cancer treatment-induced bone loss (CTIBL) is one of the most important side effects of adjuvant antineoplastic treatment in hormone-dependent neoplasms. Chemotherapy, GnRH analogs and tamoxifen can induce marked bone loss in premenopausal women with early breast cancer. Aromatase inhibitors (AIs) are replacing tamoxifen as the preferred treatment for postmenopausal women. As a class effect, steroidal (exemestane) and non-steroidal (anastrozole and letrozole) AIs increase bone turnover and cause bone loss (4%-5% over 2 years). When compared to tamoxifen, the risk of getting a clinical fracture under AI treatment is increased by 35%-50%. In patients with prostate cancer, androgen deprivation therapy (ADT) increases bone turnover, reduces bone mass (4%-5% per year) and increases the fracture rate depending on the duration of therapy. Zoledronic acid can prevent accelerated bone loss induced by goserelin in premenopausal women, by letrozole in postmenopausal women and by ADT in men. More limited data indicate that weekly alendronate or risedronate could also be effective for preventing CTIBL. Initiation of therapy early, prior to the occurrence of severe osteoporosis, rather than after, may be more effective. Bisphosphonate treatment should be considered in osteoporotic but also in osteopenic patients if other risk factor(s) for fractures are present.

Rationale: At the request of a Dutch governmental organization, a multidisciplinary group of osteoporosis experts in the Netherlands published in 2002 a guideline on case finding, diagnosis, prevention and treatment of osteoporosis. These guidelines were evaluated for their validity and applicability., Methods: Analysis by 5 external osteoporosis experts using the 'Appraisal of Guidelines for Research & Evaluation' ('AGREE') instrument., Results: The score for the 6 domains of AGREE was 88% for the scope and purpose domain, 76% for stakeholder involvement, 81% for rigour of development, 84% for clarity and presentation, 77% for applicability and 73% for editorial independence. For single components of the domains of AGREE, highest scores were found for systematic methods used to search for evidence (100%), inclusion of individuals from all the relevant professional groups (95%) and ease of identifying key recommendations (95%). Lowest scores to single components of the several domains were given for piloting among target users (44%). All experts recommended the guidelines for use in practice., Conclusions: The AGREE instrument scored high for development, clarity and presentation but low for piloting among target users and implementation. Based on the guideline, algorithms from case finding to treatment were constructed that could be tested for piloting among target users and for implementation of the guideline.

Glucocorticoids (GCs) are frequently prescribed for various inflammatory and/or life-threatening conditions concerning many systems in the body. However, they can provoke many aftereffects, of which osteoporosis (OP) is one of the most crippling complications, with its host of fractures. The dramatic increase in bone fragility is mainly attributable to the GC-induced rapid bone loss in all skeletal compartments. We have reviewed the meta-analyses and randomized controlled studies reporting medical therapeutic interventions currently registered in Belgium for the management of GC-OP comparatively with a placebo. Based on this research, an expert meeting developed a consensus on the prevention and therapy of GC-OP. The pathophysiology of GC-OP is complex. Several factors, acting separately or synergistically, have been described. Their great number could help to understand the rapidity of bone loss and of bone fragility occurrence, indicating that a rapid therapeutic intervention should be implemented to avoid complications. All patients on GCs are threatened with OP, so the prevention and/or therapy of GC-OP should be considered not only for postmenopausal females, but also for osteopenic premenopausal females and for males put on a daily dose of at least 7.5 mg equivalent prednisolone that is expected to last at least 3 months. Non-pharmacological interventions, such as exercise and avoidance of tobacco and alcohol, should be recommended, even if their role is not definitely settled in GC-OP prevention. Supplemental calcium and vitamin D should be considered as the first-line therapy because of the decrease in intestinal calcium absorption provoked by GCs. They also could be considered either as isolated therapy in patients taking less than 7.5 mg prednisolone daily and/or for a predicted period shorter than 3 months or as adjuvant therapy to other more potent drugs. Hormone replacement therapy could be considered in young postmenopausal females on GC, such as in postmenopausal OP, or in men with low androgen levels. Calcitonin appears to have a protective effect on trabecular bone in GC-OP, just as in postmenopausal OP. There is an increasing body of evidence supporting the antifracture efficacy of bisphosphonates, notably alendronate and risedronate. Preventative and curative therapy of GC-OP should be maintained as long as the patient is on GC treatment and could be stopped after weaning from GC, because there is more than circumstantial evidence of some recovery of BMD when GCs are stopped. There is no indication in GC-OP for any combination of two antiresorptive agents (except for calcium and vitamin D) or for an antiresorptive and an anabolic agent. There is indeed no proof that the increased costs of combined treatments will translate into increased therapeutic efficacy.

Unlabelled: We studied whether the LRP5 gene contributes to the clinical phenotype of IO in men. Mutation analysis in 66 IO men revealed a range of sequence variants, of which two missense variants were shown to be of functional relevance., Introduction: Mutations in the LDL receptor-related protein 5 (LRP5) gene have been associated with extreme bone phenotypes, which makes LRP5 a plausible candidate gene for idiopathic osteoporosis (IO)., Materials and Methods: In 66 men with IO, all 23 exons and exon-intron boundaries of the LRP5 gene were screened for mutations, and functional analyses were performed for those that were putatively involved in the phenotype., Results: Mutation analysis in the IO probands revealed five missense mutations, of which 1067C>T (S356L), 1364C>T (S455L), and 4609G>A (A1537T) were of potential functional significance because they were located in highly conserved regions of LRP5 and not found in a control panel. Segregation analysis in the respective families could not exclude their possible causality for IO. Furthermore, functional analyses clearly showed an inhibitory effect of mutations 1067C>T and 1364C>T on Wnt signal transduction. These effects are most likely caused by impaired LRP5 synthesis in the case of 1067C>T and failure of protein trafficking to the cell surface for 1364C>T., Conclusions: For 2 of 66 IO probands, a mutation in the LRP5 gene with proven functionality was found. The findings indicate that carrying an LRP5 mutation is a risk factor for IO, but that overall, IO in men is infrequently underlied by such a mutation.

Telomeres, the termini of linear chromosomes, exert a key role in the process of cellular ageing. Progressive telomere shortening is implicated in senescence in vitro and ample evidence exists to support the hypothesis that telomere length is correlated with chronological age and ageing phenotypes in vivo. In this study, we assessed whether mean telomere length of peripheral blood leukocytes predicts age-associated bone loss and/or is related to sex steroid status in an elderly healthy male population (71-86 years). Out of this population, we selected 110 samples for telomere restriction fragment (TRF) length analysis. Fasting blood was analysed for testosterone, estradiol, sex hormone binding globulin and biochemical markers of bone turnover. Also, the bioavailable fractions of sex steroids were calculated. Bone mineral density was measured at baseline and longitudinal follow-up was available for 84 men. We found that mean TRF length was inversely correlated with age (r=-0.19; P=0.049). Although no correlations were found with sex steroids or BMD at baseline, age corrected mean TRF length was associated with longitudinal bone loss for different distal forearm sites (P<0.05). Further studies are required to confirm our results, yet in this study, the predictive value of telomere length for bone loss appears to be substantial, hence underscoring the role of telomere length as a biomarker of ageing phenotypes.

Teriparatide (rhPTH[1-34]), a bone-forming agent for the treatment of osteoporosis, increases bone mineral density in men and women, and reduces the risk of fractures in women with osteoporosis. However, fracture efficacy has not yet been confirmed in men. Further, there is limited information on the effect of withdrawal of teriparatide. The purpose of this manuscript is to report on bone mineral density and vertebral fracture incidence during a 42-month observation period, from the baseline of the previously reported treatment study in men [1] through 30 months of posttreatment follow-up. Three hundred fifty-five men who were treated with once-daily self-injections of either placebo or 20 or 40 microg of teriparatide participated in the follow-up study. Bone mineral density gradually decreased following discontinuation of teriparatide therapy. However, the lumbar spine and total hip values remained significantly higher than baseline after 30 months of follow-up (p< or =0.001). Antiresorptive treatment prevented the decline and tended to further increase bone mineral density. Lateral thoracic lumbar radiographs obtained at baseline and 18 months after discontinuation of teriparatide were available for 279 men. Of these men, 11.7% assigned to placebo, 5.4% treated with teriparatide 20 microg, and 6.0% treated with teriparatide 40 microg had an incident vertebral fracture. In the combined teriparatide treated groups vs placebo, the risk of vertebral fracture was reduced 51% (nonsignificant, p=0.07). The incidence of moderate or severe fractures was significantly reduced by 83% (p=0.01). In conclusion, men who received teriparatide and who may have received follow-up antiresorptive therapy had a decreased risk of moderate and severe vertebral fractures.

We reported previously that a gender-specific defect of acquisition of lumbar bone mass plays an important role in the pathogenesis of male idiopathic osteoporosis (IO) and that there is a strong heritability of this maturational defect, which is particularly manifest in sons of men with IO. A hypothetical role of an altered sex steroid status and/or of a (TTTA)(n)- repeat polymorphism of the aromatase (CYP19) gene in male IO remains to be established. We evaluated bone mineral density (BMD) at the lumbar spine and femoral neck in 64 male IO probands (selected on the basis of a z-score of -2 or less), 21 of their sons, 41 of their brothers, and 126 healthy, age-matched controls. Serum testosterone (T), estradiol (E(2)), and SHBG levels were measured by immunoassays. Free T (FT) and free E(2) (FE(2)) levels were calculated from total T, E(2), SHBG, and albumin concentrations using a previously validated equation. Probands, sons, and brothers had lower body weight than age-matched controls, with mean differences of 5.0, 4.6, and 4.0 kg, respectively. In probands, sons, and brothers, SHBG levels were higher compared with controls. Significantly lower FE(2) levels were observed in probands and sons compared with their respective controls (P < 0.05 and P < 0.01, respectively). The brothers had nonsignificantly lower FE(2) levels compared with their controls. In the total group of sons with significantly lower FE(2) levels, tertile analysis according to lumbar spine BMD showed that only in the subgroup of sons belonging to the lowest tertile both FE(2) and FT were decreased compared with their controls. The differences in FE(2) levels in IO probands and their sons remained significant after adjustment for body mass index (BMI), even though in multivariate analyses BMI was a major determinant of BMD. The frequency distribution of the CYP19 gene (TTTA)(n)- repeat length (determined by fragment analysis, GeneScan) was not different between men with IO and their controls. In conclusion, the finding of a relative FE(2) deficit in both men with IO as well as their affected sons, even after adjustment for BMI, suggests that estrogen-related perturbances may be involved in the pathogenesis of the deficient acquisition of peak bone mass in male IO.

Background and Aims: The Belgian Social Security Institute (hereafter INAMI) proposes a list of conditions to be considered as a prerequisite for reimbursement of Bone Mineral Density (BMD) measurements. The aim of this paper was to evaluate the diagnostic accuracy of the proposed criteria for identifying osteoporosis, and to gauge how useful they are for more rational application of densitometry tests., Methods: 3748 Caucasian women aged at least 50 years old were recruited consecutively from an outpatient university center, from the database of which all relevant data corresponding to the INAMI list of clinical factors, as well as patients' age, weight and height, were collected. BMD measurements using dual X-ray absorptiometry were reported at the spine and hip regions. Diagnostic accuracy was evaluated through measures of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Additionally, from ROC analysis, benchmark values for age and body mass index were identified and then, used alone and in combination with the INAMI test, were applied to define various screening strategies. For each of them, associated costs per osteoporotic patient detected were estimated. Cost estimates refer only to the costs associated with the densitometric procedure from the perspective of the reimbursement health authorities., Results: Applying INAMI criteria for detecting osteoporosis at any of the considered sites yielded sensitivity of 68.9%, specificity of 50.7%, PPV of 42.9% and NPV of 57.3%. Comparison of incremental costs per patient of the different strategies revealed that, with 67.1 Euros, the option of opening BMD coverage to women on the basis of the INAMI conditions would be more cost-effective than mass screening (90.1 Euros) or applying the age criterion alone (70.2 Euros). However, the BMI condition seems to act as a better indicator of risk than the INAMI criteria in those meeting the age condition (35.4 Euros)., Conclusions: The accuracy of the INAMI proposal turns out to be quite unsatisfactory, and did not adequately cover the population at risk of osteoporosis. From a resource allocation perspective, the best strategy by far would be to recommend using concomitantly INAMI, age and BMI-selective criteria. Some adaptations could enhance the usefulness of the INAMI proposals as a selective approach for BMD referral and reimbursement.

In community-dwelling elderly men over age 70 years, BioE2 was positively associated with prospectively assessed BMD changes over 4 years. The CYP19 (TTTA)n-repeat polymorphism was, moreover, an additional independent determinant of BMD changes at the distal forearm. Furthermore, the CYP19 genotype was associated with self-reported clinical fracture status. The present analyses add further evidence to the view that serum BioE2 is a determinant of bone mass in elderly men and provides an indication that the aromatase enzyme may exert a direct modulatory action on bone metabolism at the tissue level in ageing men.

The question of whether and to what extent the sex steroid deficiency in elderly men contributes to the pathogenesis of bone loss has not been fully explored. The aim of the present study was to assess the association of serum bioavailable (Bio) estradiol (E(2)) with the evolution of bone mineral density (BMD) in 214 community-dwelling men aged 71-86 yr as well as the possible modulation of estrogen effects by a tetranucleotide (TTTA)(n)-repeat polymorphism of the CYP19 gene, which encodes the aromatase enzyme that converts androgens into estrogens. BMD was measured at yearly intervals over a period of 4 yr using dual x-ray absorptiometry. Fasting blood was analyzed at baseline for testosterone (T), E(2), and SHBG; the respective bioavailable fractions, BioT and BioE(2), were calculated. Serum BioE(2) was associated with baseline BMD at different assessed skeletal sites, with correlation coefficients ranging between 0.23 and 0.37 (P < 0.001). Estimated annual percentage change of BMD (%BMD) was -0.39% [95% confidence index (CI), -0.56, -0.22] at the total hip, -0.04% (95% CI, -0.29, 0.21) at the femoral neck, and -0.37% (95% CI, -0.45, -0.29) at the total distal forearm. Higher circulating BioE(2) levels were associated with less bone loss at the forearm and the hip (P < 0.05). The CYP19 gene (TTTA)(n)-repeat length (determined by fragment analysis) was not associated with baseline BMD in the total group of elderly men. However, a significant association was observed between the CYP19 genotype and BMD change at the distal forearm; the highest bone loss was observed in subjects homozygotic for the shortest observed allele length of (TTTA)(7)-repeats (P < 0.02). The CYP19 (TTTA)(n)-repeat length was not associated with either baseline BioE(2) or the BioT/BioE(2) ratio. In multiple linear regression models, the CYP19 genotype and serum BioE(2) were determinants of %BMD change at the forearm (P < 0.05). No significant contribution of BioT to %BMD change was evident. As to fracture risk, the allele containing the shortest (TTTA)(n)-repeat length was more represented not only in elderly men with a positive personal fracture history (Pearson's chi(2) test = 4.03; df = 1; P = 0.05) but also in study subjects with a positive fracture history in their first-degree relatives (Pearson's chi(2) test = 6.48; df = 1; P = 0.01). In conclusion, the results of this prospective observational study support the view that BioE(2) is a determinant of bone density changes in elderly men and, furthermore, provide an indication that the aromatase enzyme may exert a direct modulatory action on bone metabolism at the tissue level in elderly men.

To address the issue whether deficient acquisition of bone during maturation or adult-onset bone loss is primarily to blame for idiopathic osteoporosis in men, we assessed indices of bone mineral density and size, as well as biochemical markers of bone turnover in 61 probands (ages 20-65 years) with idiopathic osteoporosis (z-score < or = -2.0 at the spine or hip), their first-degree relatives (n = 130), and age-matched controls. There was no indication of accelerated bone loss. Indeed, in probands, the observed bone deficit versus controls was unrelated to the age of probands, and indices of bone turnover were not significantly different from controls. On the other hand, a specific deficit in bone acquisition was suggested by findings of lower bone mineral density values in three generations of male and female relatives of the probands, including their offspring; bone turnover in relatives was not different from controls. The bone mineral density deficit was more pronounced in male compared with female relatives; approximately 60% of the sons had a spinal bone mineral density z-score of less than -2.0. There also was a skeletal site-specificity in probands and their male relatives with a larger areal bone mineral density deficit at the spine compared with the hip and the forearm. The deficit at the spine corresponded to a reduction of both volumetric bone mineral density and bone size; a similar less pronounced deficit in volumetric bone mineral density, but not in bone size, was observed at the femoral neck. These findings in probands and their first-degree relatives point toward a major contributory role of a genetically determined maturational defect in bone acquisition in the pathogenesis of idiopathic osteoporosis in men.

We present cross-sectional data on bone mineral density (BMD) and quantitative ultrasound (QUS) indices in an ambulatory elderly male population (n = 235). Dual X-ray absorptiometry (DXA) at the proximal femur was considered the reference assessment site and was compared with DXA at the forearm and heel and to QUS at the heel and midtibia. Correlations and weighted kappa analysis indicate an only moderate concordance of absolute values between peripheral bone assessment and total hip DXA (weighted kappas: 0.31-0.45). Discrepancies are even more important when T-scores and prevalence rates of osteoporosis are considered, owing to factors related to the reference populations used. Predictive value of peripheral measurements for osteoporosis diagnosed on the basis of hip BMD by DXA, as assessed by receiver operator characteristic analysis, was moderate and comparable for all peripheral measurements (area under the curve: 0.708-0.870), with the exception of a clearly lower predictive value for QUS at the tibia. Discrimination of male subjects with a history of at least one fragility fracture was significant for DXA at the proximal femur and QUS at the heel. It is concluded that peripheral measurements cannot be used as a substitute for hip DXA. However, they might be useful to guide patient referral for central DXA.

Bone mineral density (BMD) measurement is widely recognized as the best single tool to identify patients with a high lifetime risk of developing an osteoporosis-related fracture. However, the cost/benefit value of screening the whole population has been repeatedly challenged and demonstrated to be rather poor. In many countries, BMD scan is not or no longer reimbursed because of lack of validated criteria to identify patients who should benefit from this procedure. Based on the proposals of a nationwide expert panel, a simple questionnaire identifying historical, clinical and behavioral risk factors for osteoporosis was developed. The aim of this study was to assess the diagnostic accuracy of the proposed criteria; to determine the extent to which this questionnaire could be useful for optimizing the use of densitometry tests; and, more specifically, to estimate the diagnostic costs per osteoporotic or osteopenic patient detected. For this purpose, we applied the questionnaire to 3998 consecutive individuals at least 20 years old, of both genders, either consulting spontaneously or referred for a BMD measurement to an outpatient osteoporosis center. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and at the hip (both total hip and femoral neck). Diagnostic accuracies were evaluated through measures of sensitivity, specificity, and positive and negative predictive values. After determining a benchmark value for age, different strategies were compared in order to identify the most cost-effective one in terms of cost per patient detected. According to the WHO operational definition of osteoporosis (T-score <-2.5), 31% of the subjects were classified as osteoporotic at one or more of the measured sites. If only patients with at least one of the proposed risk factors had been referred for scans, 33.3% of the BMD measurements would have been avoided. Among those, less than 5% were missclassified as they did have osteoporosis at the total hip and up to 23% at one or more of the considered sites. On the other hand, of the subjects who would be recommended for a densitometry test, only a small fraction were identified correctly (the positive predictive values varied from 11.3% at the total hip to 34.8% at any site). In this first setting, the suggested criteria seem useful chiefly for excluding subjects who do not need a DXA scan rather than selecting osteoporotic patients. When applied only to patients aged 61 years or more, the positive predictive values rose to 15.1% (total hip) and 42.9% (any site), whereas the corresponding negative predictive values were set at 93% and 68.6%. In comparison, with a mass screening scenario the estimated diagnostic costs (costs associated with the DXA procedure) per osteoporotic patient detected at any of the considered sites would be reduced by more than 9% (59.4 instead of 65.3 Euros) if the suggested indications are taken into account for prescreening patients. And when the questionnaire is applied only to women over the age of 60 years these costs would be further reduced to 50.6 Euros, representing a 23% decrease. Then, a prescreening strategy based on these indications concomitantly with an age-selective criterion could represent a promising way toward a more rational use of BMD measurement.

Our study was designed to establish whether the degree of osteoporosis of the distal forearm affects the outcome of distal radius fractures in elderly women. We assessed the Gartland and Werley score, wrist mobility, grip strength, ulnar variance, radial inclination and palmar tilt of both wrists in 27 postmenopausal women who had sustained a unilateral distal radius fracture following a simple fall. Bone mineral density of the contralateral uninjured wrist and mid-tibial ultrasound velocity were measured. The Gartland and Werley score, wrist mobility, loss of grip strength and the radiological results of the fractured wrist did not correlate with bone mineral density of the uninjured distal radius or with mid-tibial ultrasound velocity. These results may indicate that the influence of osteoporosis on the radiological and clinical outcome in distal radius fractures is not very important.

Background: Osteoporosis is a common complication of long-term glucocorticoid therapy for which there is no well-proved preventive or restorative treatment., Methods: We carried out two 48-week, randomized, placebo-controlled studies of two doses of alendronate in 477 men and women, 17 to 83 years of age, who were receiving glucocorticoid therapy. The primary end point was the difference in the mean percent change in lumbar-spine bone density from base line to week 48 between the groups. Secondary outcomes included changes in bone density of the hip, biochemical markers of bone turnover, and the incidence of new vertebral fractures., Results: The mean (+/-SE) bone density of the lumbar spine increased by 2.1+/-0.3 percent and 2.9+/-0.3 percent, respectively, in the groups that received 5 and 10 mg of alendronate per day (P<0.001) and decreased by 0.4+/-0.3 percent in the placebo group. The femoral-neck bone density increased by 1.2+/-0.4 percent and 1.0+/-0.4 percent in the respective alendronate groups (P<0.01) and decreased by 1.2+/-0.4 percent in the placebo group (P<0.01). The bone density of the trochanter and total body also increased significantly in the patients treated with alendronate. There were proportionally fewer new vertebral fractures in the alendronate groups (overall incidence, 2.3 percent) than in the placebo group (3.7 percent) (relative risk, 0.6; 95 percent confidence interval, 0.1 to 4.4). Markers of bone turnover decreased significantly in the alendronate groups (P<0.001). There were no differences in serious adverse effects among the three groups, but there was a small increase in nonserious upper gastrointestinal effects in the group receiving 10 mg of alendronate., Conclusions: Alendronate increases bone density in patients receiving glucocorticoid therapy.

Osteoporosis is a well-recognized adverse effect of corticosteroid therapy. This study aimed to investigate the effect of etidronate, intermittent cyclical therapy, in the prevention of corticosteroid-induced bone loss. Patients with various medical conditions starting high-dose corticosteroid therapy were enrolled in the study. The treatment had to be expected to continue for at least 12 months with the initial 90 days at a mean daily dose of at least 7.5 mg of prednisone, with subsequent treatment of at least 2.5 mg/day. One hundred seventeen patients were randomly assigned oral etidronate 400 mg/day, or placebo, for 14 days, followed by 76 days of oral calcium carbonate (500 mg elemental calcium), cycled over 12 months. The primary outcome measure was the difference in percent change from baseline in bone mineral density of the lumbar spine between the groups at the end of year 1. Secondary measures included changes in femur bone density and in biochemical markers of bone remodeling. The mean (+/- SEM) lumbar spine bone density changed 0.30 +/- 0.61% and -2.79 +/- 0.63% in the etidronate and placebo groups, respectively. The mean difference between groups after 1 yr was 3.0 +/- 0.84% (P = 0.004). The changes in the femoral neck and great trochanter were not different between the groups. There was a decrease in pyridinium crosslinks, significant from baseline at both 6 and 12 months, in the etidronate group. Osteocalcin increased in the placebo group, and difference between groups was -25.07 +/- 14.89% (P = 0.032) and -34.68 +/- 19.77% (P = 0.051), at 6 and 12 months respectively. There was no significant difference between the groups in number of adverse experiences, including gastrointestinal disorders. Etidronate intermittent cyclical therapy prevents lumbar vertebral bone loss in patients starting high-dose corticosteroid therapy.

Summary: Vertebral fractures are independent risk factors for vertebral and nonvertebral fractures. Since vertebral fractures are often missed, the relatively new introduction of vertebral fracture assessment (VFA) for imaging of the lateral spine during DXA-measurement of the spine and hips may contribute to detect vertebral fractures. We advocate performing a VFA in all patients with a recent fracture visiting a fracture liaison service (FLS). Fracture liaison services (FLS) are important service models for delivering secondary fracture prevention for older adults presenting with a fragility fracture. While commonly age, clinical risk factors (including fracture site and number of prior fracture) and BMD play a crucial role in determining fracture risk and indications for treatment with antiosteoporosis medications, prevalent vertebral fractures usually remain undetected. However, vertebral fractures are important independent risk factors for future vertebral and nonvertebral fractures. A development of the DXA technology, vertebral fracture assessment (VFA), allows for assessment of the lateral spine during the regular DXA bone mineral density measurement of the lumbar spine and hips. Recent approaches to the stratification of antiosteoporosis medication type according to baseline fracture risk, and differences by age in the indication for treatment by prior fracture mean that additional information from VFA may influence initiation and type of treatment. Furthermore, knowledge of baseline vertebral fractures allows reliable definition of incident vertebral fracture events during treatment, which may modify the approach to therapy. In this manuscript, we will discuss the epidemiology and clinical significance of vertebral fractures, the different methods of detecting vertebral fractures, and the rationale for, and implications of, use of VFA routinely in FLS. Summary points: • Vertebral fracture assessment is a tool available on modern DXA instruments and has proven ability to detect vertebral fractures, the majority of which occur without a fall and without the signs and symptoms of an acute fracture. • Most osteoporosis guidelines internationally suggest that treatment with antiosteoporosis medications should be considered for older individuals (e.g., 65 years +) with a recent low trauma fracture without the need for DXA. • Younger individuals postfracture may be risk-assessed on the basis of FRAX® probability including DXA and associated treatment thresholds. • Future fracture risk is markedly influenced by both site, number, severity, and recency of prior fracture; awareness of baseline vertebral fractures facilitates definition of true incident vertebral fracture events occurring during antiosteoporosis treatment. • Detection of previously clinically silent vertebral fractures, defining site of prior fracture, might alter treatment decisions in younger or older FLS patients, consistent with recent IOF-ESCEO guidance on baseline-risk-stratified therapy, and provides a reliable baseline from which to define new, potentially therapy-altering, vertebral fracture events. [ABSTRACT FROM AUTHOR]

Summary: There is an increasing awareness of sarcopenia in older people. We applied machine learning principles to predict mortality and incident immobility in older Belgian men through sarcopenia and frailty characteristics. Mortality could be predicted with good accuracy. Serum 25-hydroxyvitamin D and bone mineral density scores were the most important predictors.Introduction: Machine learning principles were used to predict 5-year mortality and 3-year incident severe immobility in a population of older men by frailty and sarcopenia characteristics.Methods: Using prospective data from 1997 on 264 older Belgian men (n = 152 predictors), 29 statistical models were developed and tuned on 75% of data points then validated on the remaining 25%. The model with the highest test area under the curve (AUC) was chosen as the best. From these, ranked predictor importance was extracted.Results: Five-year mortality could be predicted with good accuracy (test AUC of.85 [.73;.97], sensitivity 78%, specificity 89% at a probability cut-off of 22.3%) using a Bayesian generalized linear model. Three-year incident severe immobility could be predicted with fair accuracy (test AUC.74 [.57;.91], sensitivity 67%, specificity 78% at a probability cut-off of 14.2%) using a multivariate adaptive regression splines model. Serum 25-hydroxyvitamin D levels and hip bone mineral density scores were the most important predictors of mortality, while biochemical androgen markers and Short-Form 36 Physical Domain questions were the most important predictors of immobility. Sarcopenia assessed by lean mass estimates was relevant to mortality prediction but not immobility prediction.Conclusions: Using advanced statistical models and a machine learning approach 5-year mortality can be predicted with good accuracy using a Bayesian generalized linear model and 3-year incident severe immobility with fair accuracy using a multivariate adaptive regression splines model. [ABSTRACT FROM AUTHOR]

Summary: In an open-label extension study, BMD increased continuously with strontium ranelate over 10 years in osteoporotic women ( P < 0.01). Vertebral and nonvertebral fracture incidence was lower between 5 and 10 years than in a matched placebo group over 5 years ( P < 0.05). Strontium ranelate's antifracture efficacy appears to be maintained long term. Introduction: Strontium ranelate has proven efficacy against vertebral and nonvertebral fractures, including hip, over 5 years in postmenopausal osteoporosis. We explored long-term efficacy and safety of strontium ranelate over 10 years. Methods: Postmenopausal osteoporotic women participating in the double-blind, placebo-controlled phase 3 studies SOTI and TROPOS to 5 years were invited to enter a 5-year open-label extension, during which they received strontium ranelate 2 g/day ( n = 237, 10-year population). Bone mineral density (BMD) and fracture incidence were recorded, and FRAX® scores were calculated. The effect of strontium ranelate on fracture incidence was evaluated by comparison with a FRAX®-matched placebo group identified in the TROPOS placebo arm. Results: The patients in the 10-year population had baseline characteristics comparable to those of the total SOTI/TROPOS population. Over 10 years, lumbar BMD increased continuously and significantly ( P < 0.01 versus previous year) with 34.5 ± 20.2% relative change from baseline to 10 years. The incidence of vertebral and nonvertebral fracture with strontium ranelate in the 10-year population in years 6 to 10 was comparable to the incidence between years 0 and 5, but was significantly lower than the incidence observed in the FRAX®-matched placebo group over 5 years ( P < 0.05); relative risk reductions for vertebral and nonvertebral fractures were 35% and 38%, respectively. Strontium ranelate was safe and well tolerated over 10 years. Conclusions: Long-term treatment with strontium ranelate is associated with sustained increases in BMD over 10 years, with a good safety profile. Our results also support the maintenance of antifracture efficacy over 10 years with strontium ranelate. [ABSTRACT FROM AUTHOR]