Effects of Intermittent Parathyroid Hormone Administration on Bone Mineralization Density in Iliac Crest Biopsies from Patients with Osteoporosis: A Paired Study before and after Treatment

Abstract

Anabolic effects of PTH have been observed at several skeletal sites in humans by dual x-ray absorptiometry without differentiating between an actual increase in bone volume and an increase in mineral content within already established bone. The present study addressed this issue by evaluating the bone mineralization density distribution of iliac crest bone biopsies before and after PTH treatment for 18-36 months in men and women with osteoporosis using quantitative backscattered electron imaging. In cortical bone, pairwise comparison of the two biopsies before and after treatment revealed a reduction in the typical calcium concentration in men (-3.32%; P = 0.02, by paired t test), but no change in women, and the heterogeneity of mineralization increased in both males and females [+18.80% (P = 0.09) and +18.14% (P = 0.005), respectively]. In cancellous bone, there was no change in the typical calcium concentration, but there was a greater heterogeneity of mineralization in both men and women [+19.65% (P = 0.02) and +21.59% (P = 0.056), respectively] due to newly formed bone matrix. Small angle x-ray scattering performed on a subgroup of subjects revealed normal collagen/mineral structure. The findings confirm the observations that PTH stimulates skeletal remodeling, resulting in an increased percentage of newly formed bone matrix of lower mineral density.

Effects of 1 year of daily teriparatide treatment on iliacal bone mineralization density distribution (BMDD) in postmenopausal osteoporotic women previously treated with alendronate or risedronate

“…The teriparatide-induced increase in Ca Width even above normal in cancellous bone and the increase in cortical bone in this study are comparable with that reported previously in one study on patients who were naive to bisphosphonate treatment. (24) In this previous work, (24) as well as in a second study in bisphosphonate-naive patients, (25) teriparatide also decreased the average mineral content of the bone material, which was not seen in this study cohort. It is not clear whether this difference was due to the prior bisphosphonate treatment or to the shorter period of teriparatide treatment (12 months in this study versus 18 to 36 months in the previous study).…”

“…Further, larger effects on cortical BMDD have been described for osteoporotic women who continued hormone-replacement therapy during PTH treatment. (24) No differential effects of teriparatide treatment on BMDD between priorRIS versus priorALN…”

“…(22) The anabolic agent PTH, on the other hand, is known to decrease bone mineralization homogeneity and mineralization densities consistent with the increase in bone turnover. (23)(24)(25) In this study, we analyzed BMDD in transiliac biopsies from participants of the OPTAMISE study. The objective of our study was to evaluate the effects of sequential antiresorptive and anabolic treatment on BMDD, as well as any differences in the BMDD response to teriparatide owing to the previous bisphosphonate therapy.…”

Effects of Cyclic Versus Daily hPTH(1-34) Regimens on Bone Strength in Association With BMD, Biochemical Markers, and Bone Structure in Mice

“…This could be partly explained by the fact that mineral continues to be deposited within newly formed bone during the second week of treatment without further increases in bone volume, but resulting in a significant increase in BMD. (35)(36)(37) Another possible explanation could lie in differences in osteoblast and osteoclast activity in response to PTH withdrawal. In young male rats, Gunness-Hey et al (10) reported that the PTH-stimulated osteoblast surface remained at 50% of its maximally activated status even at 12 days after PTH discontinuation, whereas the PTH-stimulated osteoclast surface returned to the control level by 8 days after discontinuation.…”

Expression of Rho GDIα in rat osteoblasts intermittently exposed to parathyroid hormone in vitro and in vivo

“…PTH possesses bi-directional actions, ie, it is bone-catabolic and bone-anabolic. Many experiments have shown that continuous exposure to PTH decreases bone mass by stimulating a net increase in bone resorption, whereas intermittent administration of PTH can increase bone mass [1][2][3][4] . The mechanism involved in osteogenesis of intermittent PTH administration is not clear.…”