title: Daily parathyroid hormone 1-34 replacement therapy for hypoparathyroidism induces marked changes in bone turnover and structure.
abstract: Parathyroid hormone (PTH) has variable actions on bone. Chronically increased PTH is catabolic and leads to osteoporosis; yet intermittent administration is anabolic and increases bone mass. PTH deficiency is associated with decreased bone remodeling and increased bone mass. However, the effects of PTH replacement therapy on bone in hypoparathyroidism are not well known. We discontinued calcitriol therapy and treated 5 hypoparathyroid subjects (2 adults and 3 adolescents) with synthetic human PTH 1-34 (hPTH 1-34), injected two to three times daily for 18 months, with doses individualized to maintain serum calcium at 1.9 to 2.25 mmol/L. Biochemical markers and bone mineral density (BMD) were assessed every 6 months; iliac-crest biopsies were performed before and after 1 year of treatment. hPTH 1-34 therapy significantly increased bone markers to supranormal levels. Histomorphometry revealed that treatment dramatically increased cancellous bone volume and trabecular number and decreased trabecular separation. Changes in trabecular width were variable, suggesting that the increase in trabecular number was due to the observed intratrabecular tunneling. Cortical width remained unchanged; however, hPTH 1-34 treatment increased cortical porosity. Cancellous bone remodeling was also stimulated, inducing significant changes in osteoid, mineralizing surface, and bone formation rate. Similar changes were seen in endocortical and intracortical remodeling. BMD Z-scores were unchanged at the spine and femoral neck. Total hip Z-scores increased; however, total body BMD Z-scores decreased during the first 6 months of treatment and then stabilized, remaining significantly decreased compared to baseline. Radial Z-scores also decreased with treatment; this was most pronounced in the growing adolescent. Daily hPTH 1-34 therapy for hypoparathyroidism stimulated bone turnover, increased bone volume, and altered bone structure in the iliac crest. These findings suggest that treatment with hPTH 1-34 in hypoparathyroid adults and adolescents has varying effects in the different skeletal compartments, leading to an increase in trabecular bone and an apparent trabecularization of cortical bone.
authors.affiliation: Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4320, USA. gafnir@mail.nih.gov
authors.forename: Rachel I
authors.initials: RI
authors.lastname: Gafni
authors.forename: Jaime S
authors.initials: JS
authors.lastname: Brahim
authors.forename: Panagiota
authors.initials: P
authors.lastname: Andreopoulou
authors.forename: Nisan
authors.initials: N
authors.lastname: Bhattacharyya
authors.forename: Marilyn H
authors.initials: MH
authors.lastname: Kelly
authors.forename: Beth A
authors.initials: BA
authors.lastname: Brillante
authors.forename: James C
authors.initials: JC
authors.lastname: Reynolds
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: David W
authors.initials: DW
authors.lastname: Dempster
authors.forename: Michael T
authors.initials: MT
authors.lastname: Collins
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016723:Bone Remodeling / Q000187:drug effects; D003720:Densitometry; D004334:Drug Administration Schedule; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007011:Hypoparathyroidism / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology* / Q000652:urine; D007085:Ilium / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects; D010281:Parathyroid Hormone / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D016062:Porosity / Q000187:drug effects; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010281:Parathyroid Hormone