Denosumab improves trabecular bone score in relationship with decrease in fracture risk of women exposed to aromatase inhibitors.

PURPOSE: Trabecular bone score (TBS) is a gray-level textural metric that has shown to correlate with risk of fractures in several forms of osteoporosis. The value of TBS in predicting fractures and the effects of bone-active drugs on TBS in aromatase inhibitors (AIs)-induced osteoporosis are still largely unknown. The primary objective of this retrospective study was to assess the effects of denosumab and bisphosphonates (BPs) on TBS and vertebral fractures (VFs) in women exposed to AIs. METHODS: 241 consecutive women (median age 58 years) with early breast cancer undergoing treatment with AIs were evaluated for TBS, bone mineral density (BMD) and morphometric VFs at baseline and after 18-24 months of follow-up. During the study period, 139 women (57.7%) received denosumab 60 mg every 6 months, 53 (22.0%) BPs, whereas 49 women (20.3%) were not treated with bone-active drugs. RESULTS: Denosumab significantly increased TBS values (from 1.270 to 1.323; P < 0.001) accompanied by a significant decrease in risk of VFs (odds ratio 0.282; P = 0.021). During treatment with BPs, TBS did not significantly change (P = 0.849) and incidence of VFs was not significantly different from women untreated with bone-active drugs (P = 0.427). In the whole population, women with incident VFs showed higher decrease in TBS vs. non-fractured women (P = 0.003), without significant differences in changes of BMD at any skeletal site. CONCLUSIONS: TBS variation predicts fracture risk in AIs treated women. Denosumab is effective to induce early increase of TBS and reduction in risk of VFs.

Bariatric Surgery Should Be Proposed in Certain Septuagenarian Patients with Obesity.

Bariatric surgery (BS) is rarely performed on patients aged 70 and over, due to the fear of adverse effects, particularly related to sarcopenia. We examined the outcome of obese patients who underwent BS after the age of 69 in the French population. Operated subjects were matched with non-operated obese patients (n = 1307 in each group after matching). We showed that BS was associated with a reduction in mortality and no increase in the risks of rehospitalization or fracture events.

Vitamin D: 100 years of discoveries, yet controversy continues.

Over the past 100 years, many major breakthroughs and discoveries have occurred in relation to vitamin D research. These developments include the cure of rickets in 1919, the discovery of vitamin D compounds, advances in vitamin D molecular biology, and improvements in our understanding of endocrine control of vitamin D metabolism. Furthermore, recommended daily allowances for vitamin D have been established and large clinical trials of vitamin D, aimed at clarifying the effect of Vitamin D in the prevention of multiple diseases, have been completed. However, disappointingly, these clinical trials have not fulfilled the expectations many had 10 years ago. In almost every trial, various doses and routes of administration did not show efficacy of vitamin D in preventing fractures, falls, cancer, cardiovascular diseases, type 2 diabetes, asthma, and respiratory infections. Although concerns about side-effects of long-term high-dose treatments, such as hypercalcaemia and nephrocalcinosis, have been around for four decades, some trials from the past 5 years have had new and unexpected adverse events. These adverse events include increased fractures, falls, and hospitalisations in older people (aged >65 years). Several of these clinical trials were powered appropriately for a primary outcome but did not include dose response studies and were underpowered for secondary analyses. Furthermore, more attention should be paid to the safety of high doses of vitamin D supplementation, particularly in older people. In addition, despite universal recommendations by osteoporosis societies for combining calcium supplements with vitamin D there remains insufficient data about their efficacy and effect on fracture risk in the highest risk groups. More trials are needed for people with severe vitamin D deficiency (ie, serum 25-hydroxyvitamin D <25nmol/L [10ng/mL]). In this Personal View, we summarise and discuss some of the major discoveries and controversies in the field of vitamin D.

Review of bone health in women with estrogen receptor-positive breast cancer receiving endocrine therapy.

In estrogen-receptor-positive tumors, adjuvant endocrine therapy has been shown to be highly beneficial for both overall and disease-free survival. Estradiol is key in regulating bone and mineral physiology, and several studies found a strong correlation between these therapies and the risk of fractures. Since these therapies are often given for 5 through 10 years, the timing for bisphosphonates or denosumab initiation seems essential to managing bone metabolism. However, gray zones and discrepancies between guidelines remain as to the best threshold when to start antiresorptive treatment, or whether antiresorptive treatment should be administered to every woman undergoing adjuvant endocrine therapy, independent of their risk factors for fractures. Treatment options and strategies should be discussed at the start of hormone adjuvant therapy to come to a shared decision with the patient, with the final aim of reducing the risk of future fractures as much as possible. This review will cover present guidelines and literature on antiresorptive treatment in this setting, to provide clinicians with useful clues for managing these patients.

Management of bone loss due to endocrine therapy during cancer treatment.

Bone modifying agents BMAs (oral and IV bisphosphonates, denosumab) are used to treat bone loss due to endocrine therapy in patients with hormone receptor positive (HR +) early breast cancer and non-metastatic prostate cancer (NMPC). Timely initiation of appropriate sequential therapy is imperative to reduce cancer treatment-induced bone loss (CTIBL). This narrative review summarizes current literature regarding management of CTIBL in HR + early breast cancer and NMPC patients. Risk factors for fragility fractures, screening strategies, optimal timing for the treatment, dosing/duration of therapy, and post treatment monitoring have not been clearly defined in HR + early breast and NMPC patients receiving endocrine therapy. This review aims to discuss the utility of fracture risk assessment (FRAX) tool for the prevention and management of CTIBL, osteoanabolic therapy for imminent fracture risk reduction, and sequential therapy options. Using predefined terms, PubMed, MEDLINE, and Google Scholar were searched for studies on CTIBL in HR + breast and NMPC patients. We included randomized clinical trials, meta-analysis, evidence-based reviews, observational studies, and clinical practice guidelines. Fracture risk assessment tools (FRAX) guide therapy for osteoporosis in patients with early HR + breast cancer and NMPC. BMAs to prevent bone loss should be initiated at higher T-score than recommended by FRAX in premenopausal HR + breast cancer patients with chemotherapy-induced ovarian failure, oophorectomy and gonadotropin releasing hormone (GnRH) therapy, post-menopausal women with HR + breast cancer receiving aromatase inhibitor therapy, and NMPC patients with androgen deprivation therapy. Sequential therapy with osteoanabolic agents as first line treatment offers a potential therapeutic strategy in patients with high imminent fracture risk. Due to limited data in cancer patients regarding management of osteoporosis, a dosing schedule similar to osteoporosis is considered appropriate. Risk stratification to identify vulnerable patient population, choosing the appropriate sequential therapy, and close monitoring of patients at the risk of bone loss can potentially reduce the mortality, morbidity, and health care cost related to CTIBL.

Bisphosphonates for osteoporosis in people with cystic fibrosis.

BACKGROUND: Osteoporosis is a disorder of bone mineralisation occurring in about one third of adults with cystic fibrosis. Bisphosphonates can increase bone mineral density and decrease the risk of new fractures in post-menopausal women and people receiving long-term oral corticosteroids. This is an updated version of a previous review. OBJECTIVES: To assess the effects of bisphosphonates on the frequency of fractures, bone mineral density, quality of life, adverse events, trial withdrawals, and survival in people with cystic fibrosis. SEARCH METHODS: We searched the Cystic Fibrosis and Genetic Disorders Group's Trials Register of references (identified from electronic database searches and hand searches of journals and abstract books) on 5 May 2022. We performed additional searches of PubMed, clinicaltrials.gov and the WHO ICTRP (International Clinical Trials Registry Platform) on 5 May 2022. SELECTION CRITERIA: Randomised controlled trials of at least six months duration studying bisphosphonates in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Authors independently selected trials, extracted data and assessed risk of bias in included studies. Trial investigators were contacted to obtain missing data. We judged the certainty of the evidence using GRADE. MAIN RESULTS: We included nine trials with a total of 385 participants (272 adults and 113 children (aged five to 18 years)). Trial durations ranged from six months to two years. Only two of the studies were considered to have a low risk of bias for all the domains.  Bisphosphonates compared to control in people with cystic fibrosis who have not had a lung transplant Seven trials included only adult participants without lung transplants, one trial included both adults and children without lung transplantation (total of 238 adults and 113 children). We analysed adults (n = 238) and children (n = 113) separately. Adults Three trials assessed intravenous bisphosphonates (one assessed pamidronate and two assessed zoledronate) and five trials assessed oral bisphosphonates (one assessed risedronate and four assessed alendronate). Bisphosphonates were compared to either placebo or calcium (with or without additional vitamin D). Data showed no difference between treatment or control groups in new vertebral fractures at 12 months (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.02 to 2.09; 5 trials, 142 participants; very low-certainty evidence) and two trials (44 participants) reported no vertebral fractures at 24 months. There was no difference in non-vertebral fractures at 12 months (OR 2.11, 95% CI 0.18 to 25.35; 4 trials, 95 participants; very low-certainty evidence) and again two trials (44 participants) reported no non-vertebral fractures at 24 months. There was no difference in total fractures between groups at 12 months (OR 0.57, 95% CI 0.13 to 2.50; 5 trials, 142 participants) and no fractures were reported in two trials (44 participants) at 24 months. At 12 months, bisphosphonates may increase bone mineral density at the lumbar spine (mean difference (MD) 6.31, 95% CI 5.39 to 7.22; 6 trials, 171 participants; low-certainty evidence) and at the hip or femur (MD 4.41, 95% 3.44 to 5.37; 5 trials, 155 participants; low-certainty evidence). There was no clear difference in quality of life scores at 12 months (1 trial, 47 participants; low-certainty evidence), but bisphosphonates probably led to more adverse events (bone pain) at 12 months (OR 8.49, 95% CI 3.20 to 22.56; 7 trials, 206 participants; moderate-certainty evidence). Children The single trial in 113 children compared oral alendronate to placebo. We graded all evidence as low certainty. At 12 months we found no difference between treatment and placebo in new vertebral fractures (OR 0.32, 95% CI 0.03 to 3.13; 1 trial, 113 participants) and non-vertebral fractures (OR 0.19, 95% CI 0.01 to 4.04; 1 trial, 113 participants). There was also no difference in total fractures (OR 0.18, 95% CI 0.02 to 1.61; 1 trial, 113 participants). Bisphosphonates may increase bone mineral density at the lumbar spine at 12 months (MD 14.50, 95% CI 12.91 to 16.09). There was no difference in bone or muscle pain (MD 3.00, 95% CI 0.12 to 75.22), fever (MD 3.00, 95% CI 0.12 to 75.22) or gastrointestinal adverse events (OR 0.67, 95% CI 0.20 to 2.26). The trial did not measure bone mineral density at the hip/femur or report on quality of life.  Bisphosphonates compared to control in people with cystic fibrosis who have had a lung transplant One trial of 34 adults who had undergone lung transplantation compared intravenous pamidronate to no bisphosphonate treatment. It did not report at 12 months and we report the 24-month data (not assessed by GRADE). There was no difference in the number of fractures, either vertebral or non-vertebral. However, bone mineral density increased with treatment at the lumbar spine (MD 6.20, 95% CI 4.28 to 8.12) and femur (MD 7.90, 95% CI 5.78 to 10.02). No participants in either group reported either bone pain or fever. The trial did not measure quality of life. AUTHORS' CONCLUSIONS: Oral and intravenous bisphosphonates may increase bone mineral density in people with cystic fibrosis, but there are insufficient data to determine whether treatment reduces fractures. Severe bone pain and flu-like symptoms may occur with intravenous bisphosphonates. Before any firm conclusions can be drawn, trials in larger populations, including children, and of longer duration are needed to determine effects on fracture rate and survival. Additional trials are needed to determine if bone pain is more common or severe (or both) with the more potent zoledronate and if corticosteroids can ameliorate or prevent these adverse events. Future trials should also assess gastrointestinal adverse effects associated with oral bisphosphonates.

Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians.

DESCRIPTION: This guideline updates the 2017 American College of Physicians (ACP) recommendations on pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults. METHODS: The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of evidence and graded them using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. AUDIENCE AND PATIENT POPULATION: The audience for this guideline includes all clinicians. The patient population includes adults with primary osteoporosis or low bone mass. RECOMMENDATION 1A: ACP recommends that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis (strong recommendation; high-certainty evidence). RECOMMENDATION 1B: ACP suggests that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis (conditional recommendation; low-certainty evidence). RECOMMENDATION 2A: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; moderate-certainty evidence). RECOMMENDATION 2B: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; low-certainty evidence). RECOMMENDATION 3: ACP suggests that clinicians use the sclerostin inhibitor (romosozumab, moderate-certainty evidence) or recombinant PTH (teriparatide, low-certainty evidence), followed by a bisphosphonate, to reduce the risk of fractures only in females with primary osteoporosis with very high risk of fracture (conditional recommendation). RECOMMENDATION 4: ACP suggests that clinicians take an individualized approach regarding whether to start pharmacologic treatment with a bisphosphonate in females over the age of 65 with low bone mass (osteopenia) to reduce the risk of fractures (conditional recommendation; low-certainty evidence).

Vitamin D in the older population: a consensus statement.

BACKGROUND: This paper reports results from the 5th International Conference "Controversies in Vitamin D" that was held in Stresa, Italy, 15-18 September 2021. The conference is part of this series that started in 2017 and has been conducted annually since. The objective of these conferences is to identify timely and controversial topics related to Vitamin D. Dissemination of the results of the conference through publications in peer-reviewed journals is an important means by which the most up to date information can be shared with physicians, investigators, and other health care professionals. Vitamin D and aging, the subject of this paper was featured at the conference. METHODS: Participants were selected to review available literature on assigned topics related to vitamin D and aging and to present their findings with illustrative material, the intent of which was to stimulate discussion and to arrive at a consensus. The presentations were directed towards the following areas: impact of aging on vitamin D production and levels; skeletal effects of vitamin D deficiency in the older population; falls and vitamin D in the aging; potential extra skeletal effects of vitamin D; and strategies to prevent vitamin D deficiency. A final topic was related to how vitamin D might influence the efficacy of vaccines for Covid-19. RESULTS: Hypovitaminosis D can lead to several skeletal and extra-skeletal outcomes. Older adults are at risk for vitamin D deficiency as both production and metabolism of vitamin D change with aging due to factors, such as reduced sun exposure and reduced production capacity of the skin. Skeletal consequences of these age-related changes can include reduced bone mineral density, osteomalacia and fractures. Potential extra-skeletal effects can include added risks for falls, reduced muscle strength, diabetes, cancer, and cardiovascular disease. Strategies to avoid these vitamin D deficiency-related negative outcomes include sun exposure, food fortification, and supplementation. While aging does not diminish sufficient reserve capacity for cutaneous vitamin D production, concerns about skin cancers and practical matters for the institutionalized elderly limit this option. Supplementation with vitamin D is the best option either pharmacologically or through food fortification. Regardless of treatment strategies, interventions to restore sufficient vitamin D status will show positive results only in those who are truly deficient. Thus, treatment goals should focus on avoiding 25(OH)D serum levels <30 nmol/l, with a goal to reach levels >50 nmol/l. CONCLUSIONS: The results of this conference has led to consensus on several issues. Vitamin D supplementation should be combined with calcium to reduce fractures in the older population. The goal for adequate Vitamin D status should be to reach a serum level of 25(OH)D >50 nmol/l. It appears that daily low-dose vitamin D regimens reduce the risk of falling, especially in the elderly, compared with infrequent, large bolus doses that may increase it. The role of Vitamin D supplementation on muscle strength remains to be clarified. On the other hand, supplementation decreases the risk of progression to T2D from prediabetes among those who are Vitamin Ddeficient. Of three possible strategies to establish vitamin D sufficiency - sunshine exposure, food fortification, and supplementation - the latter seems to be the most effective and practical in the aging population.

B vitamins and homocysteine as determinants of bone health: A literature review of human studies.

Although there are several factors related to bone diseases such as physical activity, gender (oestrogen), race/ethnicity, smoking and alcohol habits, nutrition is a modifiable risk factor that could be employed to prevent or manage the onset of bone health diseases such as osteoporosis in humans. Aside from calcium and vitamin D, B vitamins are a group of water-soluble vitamins that play a vital role in cell metabolism. In this review, current evidence on B vitamins and bone health is assessed. Clinical trials (interventions) indicate that treatment with B vitamins impact the concentrations of total plasma/serum homocysteine concentrations (tHcy); however, most studies have reported the lack of an effect of low homocysteine concentrations on bone turnover markers, bone mineral density or fracture risks. Current studies have been inconsistent in their reports on the role of B vitamins and homocysteine in bone health. More data are therefore required to show the mechanism and effect of tHcy and B vitamins on bone mineral density, bone metabolism and fracture risk.

Moxibustion as adjuvant therapy for preventing bone loss in postmenopausal women: protocol for a randomised controlled trial.

INTRODUCTION: Postmenopausal osteoporosis, caused by ageing and oestrogen deficiency, seriously threatens women's physical and mental health. Postmenopausal osteopenia is the transition from healthy bone to osteoporosis, and it may be the key period for preventing bone loss. Moxibustion, a physical therapy of Traditional Chinese Medicine, has potential benefits for osteoporosis treatment and prevention, but it has not been adequately studied. This study aims to explore the clinical effects and safety of moxibustion in delaying bone loss in postmenopausal women. METHODS AND ANALYSIS: In this parallel-design, randomised, patient-blind and assessor-blind, controlled clinical study, 150 women with osteopenia at low fracture risk will be randomly assigned to a moxibustion treatment (MT) group or a placebo-moxibustion control (PMC) group in a 1:1 ratio. In addition to the fundamental measures (vitamin D3 and calcium) as recommended by the guidelines, participants of the two groups will receive MT or PMC treatment for 42 sessions over 12 months. The primary outcome will be the bone mineral density (BMD) of the lumbar spine at the end of the 12-month treatment, and secondary outcomes will be the BMD of the femoral neck and total hip, T-scores, bone turnover markers, serum calcium levels, serum magnesium levels, serum phosphorus levels, serum parathyroid hormone levels and 25-hydroxyvitamin D levels, intensity of bone pain, quality of life, incidence of osteoporosis and fractures, usage of emergency drugs or surgery, participant self-evaluation of therapeutic effects and the rate of adverse events. All statistical analyses will be performed based on the intention-to-treat and per-protocol principle. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University (permission number: 2021-1243). The results are expected to be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2100053953.

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: It is uncertain whether hormone therapy should be used for the primary prevention of chronic conditions such as heart disease, osteoporosis, or some types of cancers. Objective: To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions. Data Sources: PubMed/MEDLINE, Cochrane Library, EMBASE, and trial registries from January 1, 2016, through October 12, 2021; surveillance through July 2022. Study Selection: English-language randomized clinical trials and prospective cohort studies of fair or good quality. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available. Main Outcomes and Measures: Morbidity and mortality related to chronic conditions; health-related quality of life. Results: Twenty trials (N = 39 145) and 3 cohort studies (N = 1 155 410) were included. Participants using estrogen only compared with placebo had significantly lower risks for diabetes over 7.1 years (1050 vs 903 cases; 134 fewer [95% CI, 18-237]) and fractures over 7.2 years (1024 vs 1413 cases; 388 fewer [95% CI, 277-489]) per 10 000 persons. Risks per 10 000 persons were statistically significantly increased for gallbladder disease over 7.1 years (1113 vs 737 cases; 377 more [95% CI, 234-540]), stroke over 7.2 years (318 vs 239 cases; 79 more [95% CI, 15-159]), venous thromboembolism over 7.2 years (258 vs 181 cases; 77 more [95% CI, 19-153]), and urinary incontinence over 1 year (2331 vs 1446 cases; 885 more [95% CI, 659-1135]). Participants using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 persons, for colorectal cancer over 5.6 years (59 vs 93 cases; 34 fewer [95% CI, 9-51]), diabetes over 5.6 years (403 vs 482 cases; 78 fewer [95% CI, 15-133]), and fractures over 5 years (864 vs 1094 cases; 230 fewer [95% CI, 66-372]). Risks, per 10 000 persons, were significantly increased for invasive breast cancer (242 vs 191 cases; 51 more [95% CI, 6-106]), gallbladder disease (723 vs 463 cases; 260 more [95% CI, 169-364]), stroke (187 vs 135 cases; 52 more [95% CI, 12-104]), and venous thromboembolism (246 vs 126 cases; 120 more [95% CI, 68-185]) over 5.6 years; probable dementia (179 vs 91 cases; 88 more [95% CI, 15-212]) over 4.0 years; and urinary incontinence (1707 vs 1145 cases; 562 more [95% CI, 412-726]) over 1 year. Conclusions and Relevance: Use of hormone therapy in postmenopausal persons for the primary prevention of chronic conditions was associated with some benefits but also with an increased risk of harms.

Recommendations for Improving Women's Bone Health Throughout the Lifespan.

Osteoporosis is a common condition in which deteriorating bone tissue results in an increased risk of low trauma fracture. Influenced by the role of estrogen in building and maintaining bone mineral density, women have different patterns of bone accrual and loss compared with men, resulting in a lower peak bone mass and a greater lifetime fracture risk. Moreover, fracture risk increases significantly in postmenopausal women who have depleted estrogen levels. Osteoporotic fractures pose serious consequences-ranging from an inability to perform basic tasks and an increased risk of repeat fracture to the need for assisted living and even death. There is also a large economic toll associated with the health care costs required for post-fracture care. The Society for Women's Health Research (SWHR) convened an interdisciplinary Bone Health Working Group to review the current state of science and practice concerning women's bone health and osteoporosis care and to explore strategies to address gaps in screening, diagnosis, and treatment of bone disease in women. Women's bone health care must shift its paradigm from one of postmenopausal and post-fracture care to a preventive model that engages touchpoints throughout the lifespan. To achieve this paradigm shift, the Working Group recommends prioritizing efforts to build public awareness and clinical education of preventive bone health care for women, increase access to screening tools, improve patient-provider communication, and treat osteoporosis using a broader risk stratification approach.

Pharmacological management, and potentially inappropriate prescriptions in patients with osteoporosis.

BACKGROUND: The treatment of osteoporosis involves medications that reduce the risk of fractures, but some medications can decrease bone density. The aim was to identify the treatments, comorbidities, and prescriptions related to reducing bone mineral density in patients with osteoporosis. RESEARCH DESIGN AND METHODS: A cross-sectional study that identified patterns of anti-osteoporotic drug prescriptions for outpatient use and potentially inappropriate prescriptions for patients with osteoporosis based on the drug-dispensing database of 8.5 million people in Colombia. All patients ≥65 years with a diagnosis of osteoporosis were included. RESULTS: A total of 16,362 patients with osteoporosis were identified. They had a median age of 74.4 years, and 47.9% received anti-osteoporotic therapy, especially bisphosphonates (41.6%), and 86.5% received calcium and/or vitamin D supplement. 41.6% of those who had a history of bone fractures were prescribed anti-osteoporotic drugs. Potentially inappropriate prescriptions, especially corticosteroids at doses greater than 5mg prednisolone equivalent (4.4%), were found in 41.4% of cases and were more common in older patients and those with a history of fractures or with cardiovascular, digestive, neurological, psychiatric or neoplastic comorbidities. CONCLUSIONS: A significant proportion of patients had potentially inappropriate prescriptions, especially older patients, those with certain comorbidities, and those receiving comedication with antirheumatic drugs.

Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults.

BACKGROUND: Vitamin D supplements are widely recommended for bone health in the general population, but data on whether they prevent fractures have been inconsistent. METHODS: In an ancillary study of the Vitamin D and Omega-3 Trial (VITAL), we tested whether supplemental vitamin D3 would result in a lower risk of fractures than placebo. VITAL was a two-by-two factorial, randomized, controlled trial that investigated whether supplemental vitamin D3 (2000 IU per day), n-3 fatty acids (1 g per day), or both would prevent cancer and cardiovascular disease in men 50 years of age or older and women 55 years of age or older in the United States. Participants were not recruited on the basis of vitamin D deficiency, low bone mass, or osteoporosis. Incident fractures were reported by participants on annual questionnaires and adjudicated by centralized medical-record review. The primary end points were incident total, nonvertebral, and hip fractures. Proportional-hazards models were used to estimate the treatment effect in intention-to-treat analyses. RESULTS: Among 25,871 participants (50.6% women [13,085 of 25,871] and 20.2% Black [5106 of 25,304]), we confirmed 1991 incident fractures in 1551 participants over a median follow-up of 5.3 years. Supplemental vitamin D3, as compared with placebo, did not have a significant effect on total fractures (which occurred in 769 of 12,927 participants in the vitamin D group and in 782 of 12,944 participants in the placebo group; hazard ratio, 0.98; 95% confidence interval [CI], 0.89 to 1.08; P = 0.70), nonvertebral fractures (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P = 0.50), or hip fractures (hazard ratio, 1.01; 95% CI, 0.70 to 1.47; P = 0.96). There was no modification of the treatment effect according to baseline characteristics, including age, sex, race or ethnic group, body-mass index, or serum 25-hydroxyvitamin D levels. There were no substantial between-group differences in adverse events as assessed in the parent trial. CONCLUSIONS: Vitamin D3 supplementation did not result in a significantly lower risk of fractures than placebo among generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass, or osteoporosis. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; VITAL ClinicalTrials.gov number, NCT01704859.).

Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club.

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.

Hormone therapy and fractures in postmenopausal women.

BACKGROUND: Fracture rates have been reported to be higher among older women living with HIV (WLWH) than HIV- women. Hormone therapy with estrogen can reduce vasomotor symptoms (VMS) associated with menopause and prevent fractures. As data are limited on the benefits of hormone therapy use in WLWH, we examined associations of hormone therapy, use and fractures. METHODS: A prospective study of 1765 (1350 WLWH and 415 HIV-) postmenopausal Women's Interagency HIV Study (WIHS) participants was performed, including self-reported hormone therapy, use and fracture data from 2003 to 2017. Proportional hazard models determined predictors of new fractures at any site or at typical fragility fracture sites (hip, spine, wrist). RESULTS: At the first postmenopausal visit, the median (IQR) age of WLWH was slightly younger than HIV- women [49.8 (46.4-53) vs. 50.7 (47.5-54), P  = 0.0002] and a smaller proportion of WLWH reported presence of VMS (17% vs. 26%, P  < 0.0001). A greater proportion of WLWH than HIV- women reported hormone therapy use (8% vs. 4%, P  = 0.007) at the first postmenopausal visit. In multivariate analyses, white race and smoking were significant predictors of incident fracture at any site but hormone therapy ( P  = 0.69) and HIV status ( P  = 0.53) were not. CONCLUSION: Our study did not find evidence of benefit or harm with regards to fracture outcomes in postmenopausal WLWH receiving hormone therapy. Further research is needed to determine whether hormone therapy has benefits beyond treatment of VMS, such as prevention of adverse aging-associated outcomes.

Modifiable risk factors for bone health & fragility fractures.

Osteoporosis is an ageing disorder characterised by poor microstructural architecture of the bone and an increase in the risk of fragility fractures, which often leads to hospitalisation and eventually a loss of mobility and independence. By 2050, it is estimated that more than 30 million people in Europe will be affected by bone diseases, and European hospitalisation alone can approximately cost up to 3.5 billion euros each year [1]. Although inherited variation in bone mineral density (BMD) is pre-determined by up to 85% [2], there is a window of opportunity to optimise BMD and reduce fracture risk through key modifiable lifestyle factors during the life course. An optimal diet rich in micronutrients, such as calcium, vitamin D, and potassium, has long been considered an important modifiable component of bone health, which is attributed to their direct roles within bone metabolism. Recently, there has been emerging evidence to suggest that protein and even an adequate intake of fruit and vegetables may also play an important role in improving BMD [3,4]. Maintaining a physically active lifestyle is not only protective from non-communicable diseases such as cardiovascular disease but it also has been shown to lessen the risk of fractures later in life, thereby making it an imperative modifiable factor for bone health, particularly as it also supports peak bone mass attainment during childhood/adolescence and can facilitate the maintenance of bone mass throughout adulthood [5]. Other key lifestyle factors that could be potentially modified to reduce the risk of osteoporosis or osteoporotic fractures later in life include smoking status, alcohol intake, and body composition [6]. Therefore, the principle aim of this review is to highlight the recent evidence pertaining to modifiable lifestyle factors that contribute to optimal bone health and the prevention of fragility fractures in later life.

[Comprehensive personalized protocol for the prevention of repeated falls in elderly and senile patients]. / Kompleksnyi personifitsirovannyi protokol profilaktiki povtornykh padenii u patsientov pozhilogo i starcheskogo vozrasta.

OBJECTIVE: To study evaluation of the effectiveness of a comprehensive personalized protocol for the prevention of repeated falls in elderly and senile patients. MATERIAL AND METHODS: Over the course of one year, 300 patients aged 60 and older who suffered two or more falls during the year were observed. Patients of group 1 (n=100) were recommended a comprehensive personalized protocol for the prevention of repeated falls, the observance of which was regularly monitored; patients of group 2 (n=100) received standard recommendations for the prevention of falls upon discharge from the hospital, the observance of which was not actively monitored; patients of group 3 (n=100) were observed by a therapist on an outpatient basis. Primary endpoints: frequency of falls, death from any cause; secondary endpoints: the frequency of fractures, the frequency of hospitalizations for any reason. RESULTS: In group 1, after a year, the frequency of falls decreased by 5 times (100% vs. 21%, p<0.0001), in groups 2 and 3 - by 38% (p=0.013) and 81% (p<0.001). There was no significant decrease in the number of all fractures in any group, but in group 3, the frequency of vertebral fractures increased during the year (p=0.029). Statistically significant positive dynamics of indicators characterizing the geriatric status has been established: walking speed, values on the basic activity scale, a short nutrition assessment scale, the results of the drawing hours test have increased, the intensity of pain has decreased. No one died in group 1, unlike 5 patients in group 2 and 8 in group 3 (p=0.011). CONCLUSION: The use of a comprehensive personalized protocol for the prevention of repeated falls can reduce the number of complications in elderly and senile patients.