Changes in Skeletal Microstructure Through Four Continuous Years of rhPTH(1–84) Therapy in Hypoparathyroidism

• Published in: Journal of bone and mineral research Vol. 35; no. 7; pp. 1274 - 1281
• Main Authors: Cusano, Natalie E, Rubin, Mishaela R, Williams, John M, Agarwal, Sanchita, Tabacco, Gaia, Tay, Donovan, Majeed, Rukshana, Omeragic, Beatriz, Bilezikian, John P
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.07.2020; Wiley Subscription Services, Inc
• Subjects: Biopsy; Bone density; BONE MICROARCHITECTURE; Bone mineral density; Bone remodeling; Computed tomography; Dual energy X-ray absorptiometry; HIGH‐RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY (HR‐PQCT); HYPOPARATHYROIDISM; Parathyroid hormone; Porosity; Radius; Spine (lumbar); Tibia; BONE MICROARCHITECTURE; HYPOPARATHYROIDISM; HIGH-RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY (HR-PQCT)
• DOI: 10.1002/jbmr.4005
• ISSN: 0884-0431

ABSTRACT Bone remodeling is reduced in hypoparathyroidism, resulting in increased areal bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA) and abnormal skeletal indices by transiliac bone biopsy. We have now studied skeletal microstructure by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) through 4 years of treatment with recombinant human PTH(1–84) (rhPTH[1–84]) in 33 patients with hypoparathyroidism (19 with postsurgical disease, 14 idiopathic). We calculated Z‐scores for our cohort compared with previously published normative values. We report results at baseline and 1, 2, and 4 years of continuous therapy with rhPTH(1–84). The majority of patients (62%) took rhPTH(1–84) 100 μg every other day for the majority of the 4 years. At 48 months, areal bone density increased at the lumbar spine (+4.9% ± 0.9%) and femoral neck (+2.4% ± 0.9%), with declines at the total hip (−2.3% ± 0.8%) and ultradistal radius (−2.1% ± 0.7%) (p < .05 for all). By HR‐pQCT, at the radius site, very similar to the ultradistal DXA site, total volumetric BMD declined from baseline but remained above normative values at 48 months (Z‐score + 0.56). Cortical volumetric BMD was lower than normative controls at baseline at the radius and tibia (Z‐scores −1.28 and − 1.69, respectively) and further declined at 48 months (−2.13 and − 2.56, respectively). Cortical porosity was higher than normative controls at baseline at the tibia (Z‐score + 0.72) and increased through 48 months of therapy at both sites (Z‐scores +1.80 and + 1.40, respectively). Failure load declined from baseline at both the radius and tibia, although remained higher than normative controls at 48 months (Z‐scores +1.71 and + 1.17, respectively). This is the first report of noninvasive high‐resolution imaging in a cohort of hypoparathyroid patients treated with any PTH therapy for this length of time. The results give insights into the effects of long‐term rhPTH(1–84) in hypoparathyroidism. © 2020 American Society for Bone and Mineral Research.