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.

Aging is a time of reduced adaptability to metabolic perturbation. This is particularly true in endocrinology which, after all, is the science of chemically regulated biologic systems. There is no evidence that equilibrium concentrations of the principal hormones are altered with age. However, the systems utilized to reach those equilibria become progressively taxed, and new equilibria may be achieved reflecting that regulatory problem. Thus, with advancing age there are significant alterations in hormone production, metabolism, and action: Some of these changes may play a role in the pathophysiology of senescence, although the evidence for that is limited. The magnitude of age-related alterations is highly variable and sex dependent. Whereas only subtle changes occur in pituitary dynamics, adrenal gland physiology, and thyroid function, the changes in glucose homeostasis, reproductive function, and calcium metabolism are more apparent. In the elderly, the interpretation of endocrine tests should reflect the nutritional status of the patient and the presence of coexisting illnesses. In this review, we describe the principles of endocrinology in the geriatric population and elaborate on the changes in specific glandular functions with aging. We also define strategies of evaluation and management protocols appropriate for the elderly with suspected endocrine dysfunction.

Endocrinology in aging

Association of osteoporotic vertebral compression fractures with impaired functional status

Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: a randomized controlled trial.

Renal bone disease 1990: an unmet challenge for the nephrologist.

In this paper we present the results of a 12-month double-blind clinical multicenter study assessing the effects of synthetic salmon cacitonin (CT) administration in a group of white postmenopausal osteoporotic women. Treated patients were given 100 MRC units of synthetic salmon CT injected i.m. in the morning every other day. Control patients received a placebo injection. All patients received 500 mg of elementary calcium p.o., b.i.d. Bone mineral content (BMC) was measured at the extreme distal radius of the nondominant arm by a dual photon bone densitometer which utilizes two radionuclides,241Am and125I, with energies of about 60 keV and 30 keV respectively. Biochemical parameters of calcium-phosphorus metabolism were also measured. After 12 months of treatment a significant mean increment of BMC and nondialyzable OHPr/creatinine values and a significant decrease of total OHPr/creatinine values were observed in the treated group, while controls showed a significant decrease in BMC values. These results, together with the observation that in some patients the decrease in total OHPr/creatinine values was not accompanied by an increment of BMC, show that long-term salmon CT treatment may be of benefit in postmenopausal osteoporosis and that the effects of CT on bone mass may be due not only to the inhibition of bone resorption but also to the stimulation of bone formation.

Effects of salmon calcitonin in postmenopausal osteoporosis: a controlled double-blind clinical study.

This study was carried out to investigate early effects of parathyroidectomy (PTx) on bone matrix collagen metabolism. Eleven patients suffering from primary hyperparathyroidism were studied by measuring urinary excretion of hydroxyproline (OHPr) and cAMP in samples collected before PTx and, on the day of surgery, at intervals of 1-3 h for the first 10 h and then at longer intervals. In six patients nondialyzable urinary OHPr and free plasma aminoacid levels were also assayed. We found that the average period required for OHPr/Cr ratio and plasma OHPr to reach normal values was longer than the mean time required for cAMP/Cr ratio to reach normal limits. In all patients the total amount of nondialyzable OHPr decreased in the first 24 h after PTx but thereafter a daily increase in the urinary excretion of nondialyzable component was seen, so that the fractional amount of nondialyzable OHPr in the fourth postoperative day (26.8 +/- 5.2 SE) was significantly higher than that of preoperative one (6.1 +/- 1.0; p less than 0.02). Our results confirm that PTx induces a reduction in the rate of bone collagen resorption and indicate that changes of OHPr/Cr ratio and free plasma OHPr values may be considered useful indices of successful parathyroid surgery, even though they lag behind those of cAMP. The different behavior of total and nondialyzable OHPr after surgery indicates that acute deficiency of parathyroid hormone induces a positive uncoupling of the two processes of bone remodeling, thus supporting the view that the acute direct effect of the hormone on bone formation is an inhibition of this process.

R. Antonelli

Papers

Effects of salmon calcitonin in postmenopausal osteoporosis: a controlled double-blind clinical study.

Acute effects of removal of parathyroid adenoma on plasma and urinary hydroxyproline levels