There has been significant progress in the management of osteoporosis in recent years, resulting in a greater choice of therapeutic interventions for the physician. Nearly all of the treatments currently available are antiresorptive agents, which prevent bone loss and, in some cases, have been shown to reduce fracture risk. Some of these agents appear to have site-specific effects in the skeleton and may therefore not protect against all types of osteoporotic fracture. However, other drugs, such as hormone replacement therapy and possibly bisphosphonates, appear to reduce fracture risk in both the spine and hip. The optimal timing and duration of therapy for osteoporosis remain to be defined and will differ between agents. There is increasing evidence that the changes in bone mass induced by treatment do not always predict the corresponding changes in fracture rate. Thus, significant reductions in fractures may occur with antiresorptive therapy despite very small changes in bone mass, while large increases in bone mass may be associated with reduced bone strength and unchanged or increased fracture rates. Finally, the demonstration that relatively short term interventions can substantially reduce fracture rates, even in the very elderly in whom bone mass is almost universally low, provides the rationale for a more aggressive approach to treatment in patients with established disease.

Prevention and management of osteoporosis. Current trends and future prospects.

Study Objective: To determine if calcitriol is an effective treatment in postmenopausal osteoporosis. Design: Double-blind, randomized clinical trial of 2 years' duration. Setting: Univers...

Calcitriol Treatment Is Not Effective in Postmenopausal Osteoporosis

Introduction AN EXCITING new era has developed in the vitamin D field with the discovery of new target tissues, mechanisms of action, and selective analogs. As a clinical counterpoint article, this review will emphasize the potential clinical applications of these new discoveries. Many of the applications to be discussed remain untested, whereas others remain in their infancy. A major reason for optimism in predicting an expanding list of therapeutic applications for the vitamin D metabolites and analogs stems from the development of analogs of calcitriol that differ in their biological effects. In particular, analogs are now available that appear to separate the effects of calcitriol on growth and differentiation from effects on intestinal calcium absorption or bone mobilization. This apparent selectivity may reflect altered pharmacokinetic properties or may involve mechanistic differences at the cellular level as well. Regardless, the development of these drugs is likely to lead to clinical applications...

Clinical counterpoint: vitamin D: new actions, new analogs, new therapeutic potential.

Calcitriol in the treatment of postmenopausal osteoporosis

The current studies were designed to characterize type IIb sodium-inorganic phosphate (Pi) cotransporter (NaPi-IIb) expression and to assess the effect of 1,25-(OH)2 vitamin D3 on NaPi-IIb gene exp...

Age-dependent regulation of rat intestinal type IIb sodium-phosphate cotransporter by 1,25-(OH)2 vitamin D3

In order to assess the long-term effects of calcitriol treatment in postmenopausal osteoporotic patients, 1.0 micrograms/d of calcitriol was administered in two divided doses for 1 to 8 years to 270 women with symptomatic, histologically proven postmenopausal osteoporosis. No calcium supplementation was given. Clinically, the treatment resulted in substantial relief from pain, with improvement of ambulancy. Intestinal calcium absorption, which was lower than normal at baseline, increased significantly and remained higher than the baseline value as long as calcitriol was administered. Urinary calcium absorption also increased, but hypercalcemia occurred, exceptionally and transiently, in only a few patients. Urinary hydroxyproline excretion did not increase, indicating that hypercalciuria was not of resorptive origin. Total-body density, determined by dual-photon total-body absorptiometry in 56 patients, showed an increase after 18 to 24 months of therapy in most cases. The occurrence of nontraumatic, clinically relevant fractures decreased noticeably as compared with the period preceding calcitriol treatment. No change occurred in renal function, and no renal stones developed. Calcitriol was an effective and safe treatment of postmenopausal osteoporosis.

Long-term treatment with calcitriol in postmenopausal osteoporosis

Serum bone Gla-protein (BGP or osteocalcin) was measured in 25 women with histologically confirmed postmenopausal osteoporosis before and during long-term treatment with 1 microgram/day of 1,25-dihydroxyvitamin D3(1,25(OH)2D3). Basal serum BGP was significantly lower in osteoporotic women (3.8 +/- 1.4 ng/ml) than in age-matched controls (6.8 +/- 2.0 ng/ml). During 1,25(OH)2D3 therapy serum BGP increased so that the mean of the values observed on treatment (4.8 +/- 1.5) was significantly higher than the mean basal value. It is known that BGP synthesis is stimulated by 1,25(OH)2D3 and that serum BGP is a specific marker of bone formation; therefore, it is possible that the low basal levels of osteocalcin we observed were related to the low serum 1,25(OH)2D concentrations reported in osteoporotic women and that the increase in BGP levels observed under 1,25(OH)2D3 treatment was a consequence of osteoblast stimulation.

Effect of a long-term treatment with 1,25-dihydroxyvitamin D3 on osteocalcin in postmenopausal osteoporosis.

Both dual-photon absorptiometry (DPA) using 153Gd and dual-energy x-ray absorptiometry (DEXA) can be used for measurement of bone mineral content (BMC) and bone mineral density (BMD) of the total skeleton and its seven major regions. The short-term precision (coefficient of variation, CV) of DEXA for total-body BMD using the medium (20 minute) and fast (10 minute) speeds was 0.34 and 0.68% in 5 normal subjects; the corresponding CV in 5 osteoporotic females were 0.70 and 1.04%. The CV for BMD using DPA was 0.82% in 8 normal subjects and 0.70% in 12 osteoporotic patients. The CV for regional BMD using DPA was similar to fast-speed DEXA, without significant differences (p NS); precision with medium-speed DEXA was superior to DPA, and the differences were statistically significant (p less than 0.05) for head, spine, trunk, ribs, and pelvis. Total-body measurements using both DPA and DEXA were done on 99 subjects (84 females and 15 males). Significant correlations (r = 0.98; p less than 0.001) were found between DEXA and DPA measurements of both BMC and BMD. There were also significant correlations (r = 0.94-0.98; p less than 0.001) between DEXA and DPA measurements of anatomic regions (head, trunk, spine, pelvis, ribs, arms, and legs). DPA and DEXA results for BMD of total skeleton, ribs, pelvis, and legs were similar (p NS), and statistically significant differences were found in head, spine, and arm measurements (p less than 0.01, p less than 0.01, and p less than 0.05, respectively); regression equations allowed adjustment of DEXA values in patients already measured with the earlier DPA method.

G. Righi

Papers

Long-term treatment with calcitriol in postmenopausal osteoporosis

Effect of a long-term treatment with 1,25-dihydroxyvitamin D3 on osteocalcin in postmenopausal osteoporosis.

Comparison of total-body measurements by dual-energy X-ray absorptiometry and dual-photon absorptiometry

Methods and clinical applications of total body absorptiometry

Methods and clinical applications of total body absorptiometry.