Effects of Parathyroid Hormone Administration on Bone Strength in Hypoparathyroidism

The microstructural skeletal phenotype of hypoparathyroidism (HypoPT), a disorder of inadequate parathyroid hormone secretion, is altered trabecular microarchitecture with increased trabecular bone volume and thickness. Using 2-D histomorphometric analysis, we previously found that 2 years of PTH(1-84) in HypoPT is associated with reduced trabecular thickness (Tb.Th) and an increase in trabecular number (Tb.N). We have now utilized direct 3-D microstructural analysis to determine the extent to which these changes may be related to bone strength. Iliac crest bone biopsies from HypoPT subjects (n = 58) were analyzed by microcomputed tomography (mu CT) and by microfinite element (mu FE) analysis. Biopsies were performed at baseline and at 1 or 2 years of recombinant human PTH(1-84) [rhPTH(1-84)]. In a subset of subjects (n = 13) at 3 months, we demonstrated a reduction in trabecular separation (Tb.Sp, 0.64 +/- 0.1 to 0.56 +/- 0.1 mm; p = 0.005) and in the variance of trabecular separation (Tb.SD, 0.19 +/- 0.1 to 0.17 +/- 0.1 mm; p = 0.01), along with an increase in bone volume/total volume (BV/TV, 26.76 +/- 10.1 to 32.83 +/- 13.5%; p = 0.02), bone surface/total volume (BS/TV, 3.85 +/- 0.7 to 4.49 +/- 1.0 mm(2)/mm(3) ; p = 0.005), Tb.N (1.84 +/- 0.5 versus 2.36 +/- 1.3 mm(-1) ; p = 0.02) and Young's modulus (649.38 +/- 460.7 to 1044.81 +/- 1090.5 N/mm(2) ; p = 0.049). After 1 year of rhPTH(1-84), Force increased (144.08 +/- 102.4 to 241.13 +/- 189.1 N; p = 0.04) and Young's modulus tended to increase (662.15 +/- 478.2 to 1050.80 +/- 824.1 N/m(2) ; p = 0.06). The 1-year change in cancellous mineralizing surface (MS/BS) predicted 1-year changes in mu CT variables. The biopsies obtained after 2 years of rhPTH(1-84) showed no change from baseline. These data suggest that administration of rhPTH(1-84) in HypoPT is associated with transient changes in key parameters associated with bone strength. The results indicate that rhPTH(1-84) improves skeletal quality in HypoPT early in treatment. (C) 2016 American Society for Bone and Mineral Research.