Explore the vast range of titles available.

Management of postmenopausal osteoporosis includes nonpharmacologic treatment (e.g., weightbearing exercise and fall-prevention strategies) and pharmacologic treatment. Bisphosphonates are considered first-line treatment in most women; benefits and rare potential risks are discussed. Foreword This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors’ clinical recommendations. Stage A 73-year-old asymptomatic white woman with a history of a Colles fracture of the left radius 10 years earlier presents for evaluation. Dual-energy x-ray absorptiometry reveals a bone mineral density (BMD) T score of −2.8 in the lumbar spine and −2.5 in the total hip. How should this case be managed? The Clinical Problem Osteoporosis results in 1.5 million fractures per year in the United States, with the vast majority occurring in postmenopausal women. The disease is characterized by skeletal fragility and microarchitectural deterioration. The conceptual definition of osteoporosis links the high risk of postmenopausal fractures to low BMD . . .

Lipids entering the gastrointestinal tract include dietary lipids (triacylglycerols, cholesteryl esters and phospholipids) and endogenous lipids from bile (phospholipids and cholesterol) and from shed intestinal epithelial cells (enterocytes). Here, we comprehensively review the digestion, uptake and intracellular re-synthesis of intestinal lipids as well as their packaging into pre-chylomicrons in the endoplasmic reticulum, their modification in the Golgi apparatus and the exocytosis of the chylomicrons into the lamina propria and subsequently to lymph. We also discuss other fates of intestinal lipids, including intestinal HDL and VLDL secretion, cytosolic lipid droplets and fatty acid oxidation. In addition, we highlight the applicability of these findings to human disease and the development of therapeutics targeting lipid metabolism. Finally, we explore the emerging role of the gut microbiota in modulating intestinal lipid metabolism and outline key questions for future research.The small intestine is a key site for the absorption of nutrients, including lipids. In this Review, the physiology and biochemistry of intestinal fat absorption during health and disease is discussed, including insights into enterocyte biology and clinical disorders of intestinal fat absorption.

Abstract Objective The objective is to formulate clinical practice guidelines for the pharmacological management of osteoporosis in postmenopausal women. Conclusions 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 writing committee deliberations. A consensus by the Writing Committee members was achieved for 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 are capable of reducing fracture rates in postmenopausal women at risk with acceptable risk-benefit and safety profiles. Management of therapies for osteoporosis in postmenopausal women.

Abstract Objective The objective is to provide an update of the 2019 Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline for the pharmacological management of osteoporosis in postmenopausal women using romosozumab. Conclusions We reviewed findings from the meta-analysis and primary clinical trials assessing the efficacy of romosozumab, a monoclonal antibody targeting sclerostin, for the prevention of fractures and concluded that this agent can be considered a treatment option for postmenopausal women at very high risk for osteoporotic fracture. The romosozumab label has a boxed warning, recommending careful consideration by the treating clinician as to cardiovascular risk profile in the individual woman who might receive this agent, since clinical trial data from an active comparator study show an imbalance in serious cardiovascular adverse events between romosozumab and alendronate.

Key Clinical Points Postmenopausal Osteoporosis Fractures and osteoporosis are common, particularly among older women, and hip fractures can be devastating. Treatment is generally recommended in 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. Bisphosphonates (generic) and denosumab reduce the risk of hip, nonvertebral, and vertebral fractures; bisphosphonates are commonly used as first-line treatment in women who do not have contraindications. 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 for fracture.

In this study involving women 50 years of age or older who were receiving bisphosphonates, the risk of atypical femur fracture was very low as compared with the number of hip and other fractures that were prevented. Risk of atypical fractures increased with longer duration of bisphosphonate use and rapidly decreased after bisphosphonate discontinuation.

A study ancillary to a large trial showed that supplemental vitamin D 3 did not lower the risk of fractures among generally healthy midlife and older adults not selected for vitamin D deficiency, low bone mass, or osteoporosis.

There is controversy over the ideal duration of bisphosphonate therapy for osteoporosis, given reports of atypical subtrochanteric fractures and osteonecrosis of the jaw. But some subgroups of patients may benefit from continuing therapy beyond 3 to 5 years. In the 21st century, osteoporosis, a disease once considered an inevitable consequence of aging, is both diagnosable and treatable. Large, randomized, controlled trials have shown that bisphosphonate therapy for 3 to 4 years is effective in reducing the risk of both nonvertebral and vertebral fractures in osteoporotic women. 1 Not surprisingly, as many as one in seven postmenopausal women in the United States have been treated with a bisphosphonate at some time. However, there is considerable controversy over the ideal duration of antiresorptive therapy, particularly since reports have emerged of atypical subtrochanteric fractures as well as osteonecrosis of the jaw during . . .

Abstract Context Adults with type 2 diabetes (T2D) have higher fracture risk compared with nondiabetics, despite having higher bone mineral density (BMD). Insulin resistance (IR) has been associated with increased BMD. It is not known if IR increases fracture risk. Objective We investigated the relationship among IR HOMA-IR, BMD, and incident nonspine fractures in nondiabetic individuals. Design Participants included 2398 community-dwelling, nondiabetic older adults (age 74 ± 3 years, 53% women, 38% black) in the Health, Aging and Body Composition Prospective Cohort Study [median follow-up: 12 (interquartile range: 6) years]. Results The cut-off values for the HOMA-IR quartiles were 1.05, 1.54, and 2.33. Total hip BMD was 0.104 g/cm2 higher in the fourth vs the first HOMA-IR quartile (P < 0.001). This difference was attenuated after adjustment for BMI (adjusted mean difference 0.007 g/cm2; P = 0.371). In unadjusted models, fracture risk was lower in those with higher HOMA-IR [hazard ratio (HR) 0.86 (95% CI 0.73 to 1.01) and 0.65 (95% CI 0.47 to 0.89) for the third and fourth quartile, respectively, vs the first quartile]. However, after adjustment for BMD and BMI, fracture risk was significantly higher in the third quartile (HR 1.19, 95% CI 1.00 to 1.41) and tended to be increased in the fourth quartile (HR 1.12, 95% CI 0.87 to 1.46) vs the first quartile. Conclusions Greater IR is associated with higher BMD in nondiabetic older adults. In contrast to the relationship between T2D and fracture risk, we did not find consistent evidence that greater IR is associated with increased fracture risk after adjustment for BMI and BMD. We found lower risk of fracture with higher insulin resistance in older adults without diabetes. This inverse association was lost after adjustment for BMI and BMD.