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Objectives To determine whether alendronate sodium treatment is associated with upper gastrointestinal (GI) tract adverse experiences (AEs)—particularly those of the stomach, duodenum, or esophagus—in the Fracture Intervention Trial, and to assess the relationship between alendronate use and upper GI tract events among women at increased risk for these outcomes. Design Randomized, double-blind, placebo-controlled trial with a mean follow-up of 3.8 years. Women were initially randomized to receive alendronate sodium, 5 mg/d, or placebo. After 2 years, the alendronate sodium dose was increased to 10 mg/d. Participants A total of 6459 women aged 54 to 81 years recruited from 11 US clinical centers. All participants had low hip bone mineral density. Women with major upper GI tract disease (recent ulcers, upper GI tract bleeding, or use of daily medication for dyspepsia) were excluded. Regular nonsteroidal anti-inflammatory drug users were not excluded. Measurements Self-reported upper GI tract AEs were ascertained by interview every 3 months. Serious upper GI tract AEs were confirmed and classified by review of hospital records and endoscopy reports, if available. Upper GI tract AEs were further analyzed in 2 specified groups—gastroduodenal and esophageal—to examine events that might be related to upper GI tract mucosal irritation. Gastric and duodenal perforations, ulcers, and bleeding events were combined for analysis of these clinically important outcomes. Results The overall incidence of upper GI tract events was similar in the alendronate and placebo groups (47.5% vs 46.2%; relative risk [RR], 1.02; 95% confidence interval [CI], 0.95-1.10). The incidence of gastroduodenal perforations, ulcers, and bleeding events was 1.6% in the alendronate group and 1.9% in the placebo group (RR, 0.86; 95% CI, 0.59-1.24). The incidence of nonspecific upper GI tract conditions, such as abdominal pain, dyspepsia, nausea, and vomiting, was also similar in the 2 groups. Esophageal events occurred in 10.0% and 9.4% of patients in the alendronate and placebo groups, respectively (RR, 1.06; 95% CI, 0.91-1.24). Esophagitis not reported as reflux was more common in the alendronate group (0.7%) than in the placebo group (0.4%), but not significantly so (RR, 1.71; 95% CI, 0.90-3.39). Alendronate use was not associated with a significant increase in upper GI tract events among women at increased risk for these events (those aged ≥75 years with previous upper GI tract disease or using nonsteroidal anti-inflammatory drugs). Conclusion In these older women, upper GI tract complaints, particularly dyspepsia and abdominal pain, were common, but alendronate treatment was not associated with an increased incidence of upper GI tract events, even in high-risk subgroups.

Background Women with new vertebral fractures have an increased risk of back pain and functional limitation because of back pain. Alendronate sodium treatment reduces the risk of new vertebral fracture by 50% in postmenopausal women with osteoporosis. Objective To determine the effect of alendronate therapy on days affected by back pain in postmenopausal women with existing vertebral fractures. Design Three-year, placebo-controlled, randomized, double-blind study. Setting Fifteen university-based research clinics in the United States. Participants A total of 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone density and a preexisting vertebral fracture. Intervention Alendronate sodium (5 mg/d for 2 years and 10 mg/d for the third year) or placebo. Main Outcome Measures Occurrence and severity of back pain, number of days with back pain, and number of days of bed rest or limited activity because of back pain during 3 years of follow-up. Results Irrespective of treatment assignment, women with new, clinically recognized vertebral fractures during follow-up had an increased risk of days of bed disability and days of limited activity because of back pain after the fracture. Women receiving alendronate reported an average of 3.2 fewer days of bed rest ( P = .001) and 11.4 fewer days of limited activity (not including days of bed rest) because of back pain ( P = .04) during follow-up than those receiving placebo. In the alendronate group, relative to the placebo group, there was a reduced risk of 1 or more bed-rest days (relative risk, 0.68; 95% confidence interval, 0.53-0.87), of 7 or more bed-rest days (0.44; 0.30-0.64), and of 7 or more limited-activity days (0.87; 0.76-0.99). There were no statistically significant differences between treatment groups in the frequency of days of back pain or increases in back-related disability between baseline and study end. Conclusion In postmenopausal women with preexisting vertebral fracture, alendronate therapy for 3 years reduced the number of days of bed disability and days of limited activity caused by back pain.

Falls are a major threat to the health of older persons. We evaluated potential risk factors for falls in 325 community-dwelling persons aged 60 years or older who had fallen during the previous year, then followed up weekly for 1 year to ascertain nonsyncopal falls and their consequences. Risk factors for having a single fall were few and relatively weak, but multiple falls were more predictable. In multivariate analyses, we found increased odds of two or more falls for persons who had difficulty standing up from a chair, difficulty performing a tandem walk, arthritis, Parkinson's disease, three or more falls during the previous year, and a fall with injury during the previous year, and for whites. The proportion of subjects with two or more falls per year increased from 0.10 for those with none or one of these risk factors to 0.69 for those with four or more risk factors. Among older persons with a history of a recent fall, the risk of multiple nonsyncopal falls can be predicted from a few simple questions and examinations. ( JAMA . 1989;261:2663-2668)

WITH THE emergence of osteoporosis as a major public health concern, increasing attention has been given to the development and testing of strategies aimed at ameliorating this condition. Although one day effective therapeutic regimens may play a major role in the treatment arsenal, current progress in this area has met with mixed success. Consequently, many researchers and policymakers support the use of exercise as a potential strategy for the prevention of osteoporotic fractures. Clearly, exercise does not carry the negative stigma often associated with other preventive interventions such as estrogen replacement, and in light of recent evidence questioning the role of calcium supplementation at the menopause, 1,2 exercise has assumed a more recognized place in the array of probable preventive strategies. The assumption that exercise prevents osteoporosis has for years been a widely held belief by many of the leading workers in the osteoporosis field 3-6 ; concordant with these views

In Reply. —Our intention in presenting a synopsis of studies dealing with exercise and bone mass was to examine critically the current understanding of this important research area as well as provide impetus for additional, more rigorous, investigation of the potential role of physical activity in the prevention and treatment of osteoporosis. However, due to the space constraints of the commentary format, we were unable to present complete findings from every study reviewed; we selectively presented what we felt were the most clinically relevant results. In the study by Simkin and coworkers, 1 it was found that distal radial integral (25% trabecular, 75% cortical) bone as measured by single-photon absorptiometry did not change significantly as a result of bone-loading exercises over the course of five months in postmenopausal women. As we reported, this finding was similar to findings reported from at least three previous prospective studies employing the same technique.