ACTIVExtend: 24 Months of Alendronate After 18 Months of Abaloparatide or Placebo for Postmenopausal Osteoporosis.

Purpose: In women with postmenopausal osteoporosis, we investigated the effects of 24 months of treatment with alendronate (ALN) following 18 months of treatment with abaloparatide (ABL) or placebo (PBO). Methods: Women who completed ABL or PBO treatment in ACTIVE were eligible to receive up to 24 months of ALN. We evaluated the incidence of vertebral and nonvertebral fractures and changes in bone mineral density (BMD) during the entire 43-month period from ACTIVE baseline to the end of ACTIVExtend and for the 24-month extension only. Results: Five hundred fifty-eight women from ACTIVE's ABL group and 581 from its PBO group (92% of ABL and PBO completers) were enrolled. During the full 43-month treatment period, 0.9% of evaluable women in the ABL/ALN group experienced a new radiographic vertebral fracture vs 5.6% of women in the PBO/ALN group, an 84% relative risk reduction (RRR, P < 0.001). Kaplan-Meier incidence rates for other reported fracture types were significantly lower for ABL/ALN vs PBO/ALN (all P < 0.05). Gains in BMD achieved during ACTIVE were further increased during ACTIVExtend. For ACTIVExtend only, RRR for vertebral fractures was 87% with ABL/ALN vs PBO/ALN (P = 0.001). Adverse events were similar between groups. A supplemental analysis for regulatory authorities found no hip fractures in the ABL/ALN group vs five in the PBO/ALN group. Conclusions: Eighteen months of ABL followed by 24 months of ALN reduced the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures and increased BMD. Sequential ABL followed by ALN appears to be an effective treatment option for postmenopausal women at risk for osteoporosis-related fractures.

Vitamin D Repletion in Korean Postmenopausal Women with Osteoporosis.

PURPOSE: Up to 71% of South Korean postmenopausal women have vitamin D deficiency {serum 25-hydroxyvitamin D [25(OH) D] level <50 nmol/L}. Data on vitamin D supplementation was collected during the screening phase of an efficacy/safety study of denosumab in Korean postmenopausal women with osteoporosis. This report describes the effect of vitamin D supplementation on repletion to 25(OH)D levels ≥50 nmol/L in Korean postmenopausal women with osteoporosis. MATERIALS AND METHODS: Vitamin D levels of Korean postmenopausal women (60-90 years old) were measured by extracting 25(OH)D2 and 25(OH)D3 from serum samples via protein precipitation and using liquid chromatography with tandem mass spectrometry detection. Calibration curves were constructed from the mass chromatograms to obtain total vitamin D levels. Subjects with serum 25(OH)D levels <50 nmol/L were supplemented with 1000 IU of vitamin D tablets during the 2.5-month-long screening period. Dose, frequency, and duration were determined by the investigator. If repletion was achieved (≥50 nmol/L) on retest, subjects were eligible to be rescreened for study entry. RESULTS: Of 371 subjects screened, 191 (52%) required vitamin D supplementation, and 88% (168 of 191) were successfully repleted. More than half of the subjects (58%) who were successfully repleted received doses of 2000 IU daily. The mean time to successful repletion was 31 days (standard deviation 8.4 days; range 11-48 days). CONCLUSION: Supplementation with daily median doses of 2000 IU vitamin D successfully repleted 88% of Korean postmenopausal women with osteoporosis within 48 days to a serum vitamin D level of 50 nmol/L.

Soy isoflavones: hope or hype?

Approximately 50% of Americans use dietary supplements on a regular basis spending an estimated $20 billion on supplements in the year 2000. Soy contains genistein and daidzein, two phytoestrogens, which work through the estrogen receptor and cause alterations in serum lipids, bone metabolism, and possibly cognition. In this article, we review the issues regarding the interpretation with studies using soy-based isoflavones, discuss their mechanism of action, and review the literature on the effect of these bio-active compounds on lipid metabolism, osteoblasts and osteoclasts, bone markers, bone mineral density, and cognition.

Alternatives to estrogen.

For many years, women have sought alternative therapies for menopausal symptoms and for general health overall. The highly publicized findings from the Women's Health Initiative have led to an increased pressure on the medical community to find safe and alternative medications for female health. This article reviews the challenges and problems with the use of alternative medicines, and the clinical trials that prove their efficacy, and discusses the safety issues that may occur with these types of products.

Phytoestrogens--mechanism of action and effect on bone markers and bone mineral density.

Dietary supplements, especially those containing phytoestrogens, frequently are used to either promote health or prevent disease. An estimated 20 billion dollars was spent on dietary supplements in the year 2000. Approximately 40% to 55% of Americans use supplements on a regular basis and 24% of these supplements contain herbs. Phytoestrogens are defined as any compound that is structurally or functionally related to ovarian or placental estrogens and their active metabolites. These compounds are widely used for various disorders related to women's health.

Soy isoflavones: hope or hype?

Approximately 50% of Americans use dietary supplements on a regular basis spending an estimated $20 billion on supplements in the year 2000. Soy contains genistein and daidzein, two phytoestrogens, which work through the estrogen receptor and cause alterations in serum lipids, bone metabolism, and possibly cognition. In this article, we review the issues regarding the interpretation with studies using soy-based isoflavones, discuss their mechanism of action, and review the literature on the effect of these bio-active compounds on lipid metabolism, osteoblasts and osteoclasts, bone markers, bone mineral density, and cognition.

Osteoporosis: alternatives to estrogen treatment.

Osteoporosis-related fractures result in significant morbidity, mortality, and cost in the United States. With the aging of our population, the cost to society and number of individuals who will become disabled by hip fractures alone could triple by the year 2040. Many known risk factors allow us to identify individuals with increased susceptibility for osteoporosis. Secondary causes of bone loss should always rigorously be ruled out in patients. Laboratory assessment and measurement of bone mineral density can help aid treatment choices. This article discusses risk factors for and secondary causes of osteoporosis, as well as radiographic and laboratory evaluation for the disease. It also presents nonestrogen treatments for osteoporosis. Lifestyle changes are an important aspect of treatment. In addition, antiresorptive and anabolic agents can markedly improve bone mineral density. Our ability to prevent fractures will be improved in the future as we are better able to assess fracture risk, measure bone strength, and provide new compounds for the prevention and treatment of bone loss.

Does bone change after biliopancreatic diversion?

This prospective study evaluated bone changes after biliopancreatic diversion (BPD) consisting of a distal gastrectomy, a 250 cm alimentary channel, and a 50 cm common channel. Thirty-three consecutive patients had clinical, biochemical, and bone mineral density analysis before surgery and 4 and 10 years after surgery. Iliac crest bone biopsies and special tests including parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25-OH(2)-D), bone-specific alkaline phosphatase (BAP), and osteocalcin were obtained at surgery and 4 years postoperatively. Over the years, with close metabolic surveillance, additional calcium and vitamin D were given as indicated. After BPD, serum levels of calcium and vitamin D were decreased and serum levels of PTH, BAP, and osteocalcin were increased. Bone turnover and mineralization were both increased. Mean osteoid volume (P < 0.0007) and bone formation rate in relation to bone volume (P < 0.02) were increased. Static measures of bone were altered as follows: cortical thickness decreased (P < 0.01) and trabecular bone volume increased (P < 0.01). Ten years after surgery, overall bone mineral density was unchanged at the hip and was decreased by 4% at the lumbar spine. Overall fracture risk, based on the Z score, was unchanged. Preoperative factors predicting bone loss included menopause, smoking, and preexisting osteopenia. An elevated level of 1,25-OH(2)-D was also found to be a predictor of future bone loss (r = 0.40; P < 0.002). After surgery, a greater increase in bone markers and bone turnover was associated with an increased risk of bone loss. Although elevated osteocalcin levels were associated with overall bone loss (r = 0.52; P < 0.002), lower albumin levels were associated only with bone loss at hip level (r = 0.44; P < 0.02), whereas lower calcium levels were associated only with the loss at the lumbar spine (r = 0.39; P < 0.02). Ten years after surgery, bone loss at the hip continued to depend on albumin levels (r = 0.37; P < 0.03). We concluded that bone was relatively tolerant to the metabolic changes due to BPD. Provided that there is close surveillance for metabolic disturbances, the use of appropriate supplements, and the avoidance of malnutrition, the beneficial effects of surgery far outweigh the risk of postoperative bone disease.