Background Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown. Methods We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 μg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry. Results New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-μg and 40-μg parathyroid hormone groups; the respective relative risks of fracture in the 20-μg and 40-μg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragili...

Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(96)07088-2.pdf

Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures

Medical practice is constantly changing. The rate of change is accelerating, and physicians can be forgiven if they often find it dizzying. How can physicians learn about new information and innovations, and decide how (if at all) they should modify their practice? Possible sources include summaries from the medical literature (review articles, practice guidelines, consensus statements, editorials, and summary articles in "throwaway" journals); consultation with colleagues who have special expertise; lectures; seminars; advertisements in medical journals; conversations with representatives from pharmaceutical companies; and original articles in journals and journal supplements. Each of these sources of information might be valuable, though each is subject to its own particular biases. 1,2 Problems arise when, as is often the case, these sources of information provide different suggestions about patient care. See also p 2093. Without a way of critically appraising the information they receive, clinicians are relatively helpless in deciding what new information

https://hopkinsmedicine.org/gim/_pdf/jama/17-screening.pdf

Users' Guides to the Medical Literature

The assessment of vertebral fracture by conventional radiography has been refined and improved using either semiquantitative or quantitative criteria. The inter- and intraobserver variability was determined for a semiquantitative visual approach that we routinely use in clinical studies for assessing prevalent and incident vertebral fractures. In addition, the semiquantitative approach was compared with a quantitative morphometric approach. The incidence and prevalence of vertebral fractures were determined in 57 postmenopausal women (age 65-75 years) by three independent observers. The radiographic basis for fracture definitions and the source of interobserver agreement for the semiquantitative technique. We conclude that the semiquantitative approach can be applied reliably in vertebral fracture assessment when performed using well-defined criteria.

Vertebral fracture assessment using a semiquantitative technique

Assessment of fracture risk and its application to screening for postmenopausal osteoporos

Progressive bone loss in osteoporosis results from bone resorption in excess of bone formation. We conducted a double-blind study in 66 women with postmenopausal osteoporosis of therapy with etidronate, a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned in equal numbers to receive oral etidronate (400 mg per day) or placebo for 2 weeks, followed by a 13-week period in which no drugs were given. This sequence was repeated 10 times, for a total of 150 weeks. Daily oral supplementation with calcium and vitamin D was given throughout the study to both groups. Vertebral bone mineral content was measured by dual-photon absorptiometry; spinal radiographs were assessed to identify new vertebral fractures. Vertebral bone mineral content increased significantly (P less than 0.01) after 150 weeks of etidronate therapy (5.3 percent; 95 percent confidence interval, 2.0 to 8.6; n = 20) but decreased with placebo (-2.7 percent; 95 percent confidence interval, -7.3 to 1.9; n = 20). The difference between groups was 8.0 percentage points (P less than 0.01; 95 percent confidence interval, 2.4 to 13.6). The rates of fracture were significantly different for the period from week 60 to week 150 between the etidronate and placebo groups (6 vs. 54 fractures per 100 patient-years; P = 0.023). No adverse clinical, biochemical, or bone histomorphometric effects of treatment were observed. We conclude that at the end of nearly three years, etidronate therapy for postmenopausal osteoporosis results in significant increases in vertebral bone mineral content and, after approximately one year of treatment, a significant decrease in the rate of new vertebral fractures.

https://www.nejm.org/doi/pdf/10.1056/NEJM199005033221803

Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis.

Objective. To evaluate the effects of 120 weeks of intermittent cyclical etidronate on the progression of bone loss and fracture incidence and rate in postmenopausal osteoporotic women after 150 weeks of either etidronate or placebo treatment. Methods. This was an open label followup study of 37 postmenopausal osteoporotic women enrolled from the earlier 150 week study, 17 from the etidronate group and 20 from the placebo group. Treatment cycles were of oral doses of etidronate 400 mg/day for 2 weeks, followed by a 13 week drug-free period for a total of 120 weeks. All patients received a daily supplement of 0.5 g calcium and 400 U vitamin D. Results. During the earlier 150 week study, mean vertebral bone mineral content increased significantly in the etidronate group by 5.5% (p = 0.013) and decreased by 2.7% (not significant) in the placebo group. After 120 weeks of etidronate treatment in this followup study, patients who had formerly received etidronate experienced an additional 1.4% increase ; after 5 years, bone mineral content was 6.9% above the original baseline (p = 0.037). Bone mineral content also increased in the former placebo group during the latter study, up to 5.3% above the original study baseline (not significant). The vertebral fracture rate in the former placebo group decreased significantly, from 103 to 27 per 100 patient-years (p < 0.01), while the fracture rate in the former etidronate group was unchanged (38 and 33 per 100 patient-years). Conclusion. Five years of etidronate therapy for postmenopausal osteoporosis results in significant increases in vertebral bone mineral content, and the previously observed reduction in vertebral fracture rate in the etidronate group is maintained during at least 5 years of therapy.

O H Sørensen

Papers

Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis.

Five years of clinical experience with intermittent cyclical etidronate for postmenopausal osteoporosis.