Osteoporosis — Are Calcium and Medication the Right Approach?

Aim of the study: The aim of the present study was to explore whether combined calcium and vitamin D supplementation is beneficial for osteoporosis in postmenopausal women.

Results: Combined calcium and vitamin D significantly increased total bone mineral density (BMD) (standard mean differences (SMD) = 0.537; 95% confidence interval (CI): 0.227 to 0.847), lumbar spine BMD (SMD = 0.233; 95% CI: 0.073 to 0.392; P < 0.001), arm BMD (SMD = 0.464; 95% CI: 0.186 to 0.741), and femoral neck BMD (SMD = 0.187; 95% CI: 0.010 to 0.364). It also significantly reduced the incidence of hip fractures (RR = 0.864; 95% CI: 0.763 to 0.979). Subgroup analysis showed that combined calcium and vitamin D significantly increased femoral neck BMD only when vitamin D intake was no more than 400 IU d-1 (SMD = 0.335; 95% CI: 0.113 to 0.558), but not at a dose above 400 IU d-1 (SMD = -0.098; 95% CI: -0.109 to 0.305), and calcium had no effect on femoral neck BMD.

Aim of the study: Calcium plus vitamin D supplementation has been widely recommended to prevent osteoporosis and subsequent fractures; however, considerable controversy exists regarding the association of such supplementation and fracture risk. The aim was to conduct a meta-analysis of randomized controlled trials [RCTs] of calcium plus vitamin D supplementation and fracture prevention in adults.

Results: Of the citations retrieved, eight studies including 30,970 participants met the criteria for inclusion in the primary analysis, reporting 195 hip fractures and 2,231 total fractures. Meta-analysis of all studies showed that calcium plus vitamin D supplementation produced a statistically significant 15% reduced risk of total fractures (SRRE, 0.85; 95% confidence interval [CI], 0.73-0.98) and a 30% reduced risk of hip fractures (SRRE, 0.70; 95% CI, 0.56-0.87). Numerous sensitivity and subgroup analyses produced similar summary associations. One limitation is that this study used data from a subgroup analysis of the Women's Health Initiative. This meta-analysis of RCTs supports the use of calcium plus vitamin D supplements to reduce fracture risk in both community-dwelling and institutionalized middle-aged to older adults.

Aim of the study: Postmenopausal osteoporosis (PMO) is a major cause of fragility fractures worldwide. While exercise and calcium/vitamin D are standard preventive measures, the synergistic effects of their combined use on bone mineral density (BMD) remain unclear.

Results: Thirteen RCTs involving postmenopausal women were included. Compared with calcium and vitamin D supplementation alone, combined interventions significantly increased lumbar spine (SMD = 0.31, 95% CI [0.06, 0.55]) and femoral neck BMD (SMD = 0.47, 95% CI [0.09, 0.84]), with consistent but nonsignificant trends at other skeletal sites. Subgroup analyses showed that whole-body vibration produced the greatest and most consistent benefits at both sites, while mind-body or traditional Chinese exercises (e.g., Baduanjin) significantly improved lumbar spine BMD. Shorter interventions (≤6 months) produced greater gains in BMD, while longer durations provided no additional benefit. Exercise combined with calcium and vitamin D supplementation effectively improves bone mineral density in postmenopausal women, especially in the lumbar spine and femoral neck. Whole-body vibration and mind-body exercises show the greatest benefits, with short-term interventions proving most effective.

Aim of the study: Key Clinical Points: Postmenopausal Osteoporosis. Fractures and osteoporosis are common, particularly among older women, and hip fractures can be devastating. Treatment is generally recommended for postmenopausal women who have a bone mineral density T score of -2.5 or less, a history of spine or hip fracture, or a Fracture Risk Assessment Tool (FRAX) score indicating increased fracture risk.

Results: Teriparatide reduces the risk of nonvertebral and vertebral fractures. Osteonecrosis of the jaw and atypical femur fractures have been reported with treatment but are rare. The benefit-to-risk ratio for osteoporosis treatment is strongly positive for most women with osteoporosis. Because benefits are retained after discontinuation of alendronate or zoledronic acid, drug holidays after 5 years of alendronate therapy or 3 years of zoledronic acid therapy may be considered for patients at lower risk of fracture.

Aim of the study: The objective is to formulate clinical practice guidelines for the pharmacological management of osteoporosis in postmenopausal women.

Results: Evidence from clinical trials and insights from clinical experience with pharmacologic therapies for osteoporosis were critically evaluated in formulating this guideline for the management of postmenopausal osteoporosis. Patient preferences, data on adherence and persistence, and risks and benefits from the patient and provider perspectives were also considered in the writing committee's deliberations. The writing committee members reached consensus on four management principles: (i) The risk of future fractures in postmenopausal women should be determined using country-specific assessment tools to guide decision-making. (ii) Patient preferences should be incorporated into treatment planning. (iii) Nutritional and lifestyle interventions and fall prevention should accompany all pharmacologic regimens to reduce fracture risk. (iv) Multiple pharmacologic therapies can reduce fracture rates in postmenopausal women at risk, with acceptable risk-benefit and safety profiles.

Aim of the study: Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation.

Results: All dose levels of romosozumab were associated with significant increases in bone mineral density in the lumbar spine, including an increase of 11.3% with the 210-mg monthly dose, compared with a decrease of 0.1% with placebo and increases of 4.1% with alendronate and 7.1% with teriparatide. Romosozumab was also associated with large increases in bone mineral density at the total hip and femoral neck, as well as temporary increases in bone-formation markers and sustained decreases in a bone-resorption marker. Except for mild, generally nonrecurring injection-site reactions with romosozumab, adverse events were similar among groups. In postmenopausal women with low bone mass, romosozumab was associated with increased bone mineral density and bone formation and decreased bone resorption. (Funded by Amgen and UCB Pharma; ClinicalTrials.gov number, NCT00896532.)

Aim of the study: The aim of this study is to provide a thorough, updated review of the diagnosis and treatment of postmenopausal osteoporosis.

Results: Several important findings in the field of postmenopausal osteoporosis have emerged over the past 1–2 years. Fewer morphometric vertebral fractures were found in women treated for 6 years with zoledronic acid compared with women who stopped treatment after 3 years. Longer durations of bisphosphonate therapy are associated with a higher risk of atypical femur fractures. Combination therapy with teriparatide and denosumab appears to increase bone mineral density more than either therapy alone in postmenopausal women at high risk of fracture. Several novel therapies for osteoporosis are under investigation at various stages of development. Nonadherence to osteoporosis therapies continues to be a major problem in clinical practice.

Aim of the study: Osteoporosis affects approximately 8 million women and 2 million men in the United States. The associated fractures are a common and preventable cause of morbidity and mortality in up to 50 percent of older women.

Results: The Preventive Services Task Force recommends using dual-energy x-ray absorptiometry to screen all women 65 years and older, and women 60 to 64 years of age who have an increased risk of fracture. Some organizations recommend considering screening for all men 70 years and older. For people with osteoporosis diagnosed by dual-energy x-ray absorptiometry or a previous fragility fracture, effective first-line treatment consists of preventing falls, adequate intake of calcium (at least 1,200 mg per day) and vitamin D (at least 700 to 800 IU per day), and treatment with a bisphosphonate. Raloxifene, calcitonin, teriparatide, or hormone therapy may be considered for certain groups of patients.

Aim of the study: Osteoporosis affects an estimated 200 million people worldwide. Fragility fractures of the hip, spine, and wrist carry high mortality and impose a heavy socioeconomic burden.

Results: Senolytic combinations and PROTAC-based degraders represent newer modes of action. This review examines the chemistry behind these compounds, their structure-activity relationships, their preclinical pharmacology, and their progress through clinical evaluation. We pay particular attention to the failures (odanacatib, calcilytics, integrin antagonists, Src inhibitors) as well as the successes, because the lessons from attrition shape the chemistry choices that follow. We attempt to identify those chemistry-led strategies that have most reliably accelerated bench-to-bedside translation in bone disease, and those that have not.

Aim of the study: Chronic kidney disease (CKD)-associated osteoporosis is present in approximately 25% of all patients with CKD. Its prevalence increases as kidney function declines, reaching up to 75% in elderly dialysis patients.

Results: Because modifiable risk factors for fragility fractures are more prevalent in CKD, non-pharmacological interventions should be provided to all patients with CKD-associated osteoporosis. We review the current literature and describe 10 tips for non-pharmacological interventions that may modify fracture risk in CKD patients: appropriate intake of calcium and vitamin D; adequate nutrition and protein intake; avoiding smoking and alcohol; reviewing medications; encouraging exercise; reducing hazards in the home; preventing orthostatic hypotension; addressing neuropathy and assessing fall risk; and implementing fracture liaison services. All of these actions are relevant for patients with CKD-associated osteoporosis. As in the general population, non-pharmacological interventions should be the first option considered when osteoporosis is diagnosed. In this paper, we suggest how these measures should be tailored to patients with CKD.