Histomorphometric evidence for increased bone turnover without change in cortical thickness or porosity after 2 years of cyclical hPTH(1-34) therapy in women with severe osteoporosis

Parathyroid hormone (PTH) increases trabecular but may decrease cortical bone mass during treatment of postmenopausal osteoporosis. in a 2-year trial, PTH, with or without sequential calcitonin (CT), was given to 29 osteoporotic women (mean age 67 +/- 7 years), in 3-month cycles [28 days hPTH (1-34), 50 mu g/day, +/-42 days CT, 75 units/day, 20 days "free"], Over 2 years, lumbar spine hone mineral density measurements increased an average of 10%. Paired iliac crest biopsies were obtained 28 days and 2 years after starting the trial. The addition of CT made no difference to changes seen with cyclical PTH alone. Thus, the histomor-phometric analyses For all 29 treated patients were compared with a separate group of biopsies from untreated osteoporotic control patients (n = 15), No significant increments in total bone volume or trabecular architecture were seen over 2 years of cyclical PTH treatment, although the light microscopic appearance of bone was normal. At the level of the bone remodeling unit, a twofold increase in total trabecular erosion surface over the control measurements was observed within the first 28 days of PTH treatment (10 +/- 5 vs. 5 +/- 3% trabecular surface, p < 0.01), which was sustained over 2 Scars. Trabecular hone formation rates (surface referent) were 11 +/- 7 mu m(3)/mu m(2)/year in control patients and threefold higher in treated patients both acutely (31 +/- 31 mu m(3)/mu m(2)/year, p < 0.01) and after 2 years (33 +/- 43 mu m(3)/mu m(2)/year, p < 0.05). The activation frequency of trabecular remodeling was threefold higher than controls through 2 years of treatment (p < 0.05). The mean wall thickness of completed osteons after 2 years of treatment was significantly larger than controls (28 +/- 7 vs. 22 +/- 5 pm, p < 0.01), suggesting a positive relnodeling balance, as well as the histomorphometric evidence of increased bone turnover and the increased resorption surfaces. Over 2 years of cyclical PTH therapy, cortical thickness remained significantly higher than controls (680 +/- 202 vs 552 +/- 218 mu m, p < 0.05), without significant changes in cortical porosity. Thus, the histomorphometric changes during cyclical PTH therapy in patients with severe osteoporosis are consistent with increased trabecular bone turnover and a positive remodeling balance, with no evidence for detrimental changes in cortical bone. (C) 2000 by Elsevier Science Inc. All rights reserved.