Effects of cyclical therapy for osteoporosis using an oral regimen of inorganic phosphate and sodium etidronate: a clinical and bone histomorphometric study.

Cyclical therapy for osteoporosis has been proposed as a means to induce a coherently structured improvement in bone remodelling dynamics. This pilot study involved 37 osteoporotic patients with symptomatic vertebral compression fractures, treated with an oral protocol designed to activate endogenous bone turnover and selectively depress osteoclastic bone resorption, utilizing inorganic phosphate and sodium etidronate respectively in sequential 3 monthly cycles. Biochemical parameters were recorded during the first cycle, and quantitative bone histomorphometry was obtained from iliac crest biopsies before and after 23.4 +/- 8.5 (SEM) months of treatment. In addition, fracture rates (expressed as new vertebral fractures/1000 patient years) were studied by sequential lateral spinal radiographs. Lumbar bone mineral density (BMD) was assessed by sequential dual-beam photon densitometry. The results demonstrated equivocal biochemical evidence of 2 degrees hyperparathyroidism during the initial cycle of therapy with inorganic phosphate. However, fracture rates declined significantly from 640/1000 patient years during the first 15 months therapy to 242/1000 patient years during a further 20 months follow-up (P less than 0.01). Lumbar BMD increased over baseline by 8.38 +/- 2.87% after 12 months treatment (P less than 0.01). Bone histomorphometric analysis disclosed a modest increment in bone volume from 16.0 to 17.4% tissue volume, and a significant increase in eroded surface from 4.2 +/- 0.6 to 6.0 +/- 0.9% cancellous surface (P less than 0.05). However, histomorphometric parameters of bone formation deteriorated. It is concluded that this cyclical protocol resulted in short-term improvement in trabecular bone mass, but there is no evidence at a cellular level that long-term improvements in bone remodelling occurred.