A Pilot Study of Cognition Among Hypoparathyroid Adults.

PURPOSE: Hypoparathyroid patients describe cognitive deficits, yet data regarding objective assessment of cognitive function are limited. We assessed cognition in a pilot study of hypoparathyroid patients using the National Institutes of Health Toolbox® Adult Cognitive Battery (NIHTB-CB). We also sought to determine whether cognition relates to emotion, quality of life, and hypoparathyroidism-related biochemistries. METHODS: Nineteen hypoparathyroid patients were studied. Objective cognition was assessed with NIHTB-CB. Impairment was defined as fully demographically adjusted T-score < 1.5 SD in at least 1 cognitive domain or < 1 SD in 2 or more domains. RESULTS: Of the 19 participants (17 women; median age 49; 18 postsurgical), impaired demographically adjusted NIHTB-CB cognition scores were observed in 13 subjects (68%). Cognition scores correlated with self-reported perception of general health. Processing speed was the most commonly impaired cognitive domain, with T-scores that were ≤2 SD in 6 subjects (32%). Processing speed correlated with serum calcium (r = 0.53, P = 0.023) and inversely with serum phosphate (r = -0.48, P = 0.042) levels. CONCLUSIONS: Impaired cognition using the NIHTB-CB was common in this small pilot cohort of hypoparathyroid patients. Slower processing speed was present and associated with lower serum calcium and higher serum phosphate levels. Larger controlled studies with additional neuropsychological testing are needed to investigate cognitive function in hypoparathyroidism.

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

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.

Therapy of Hypoparathyroidism With rhPTH(1-84): A Prospective, 8-Year Investigation of Efficacy and Safety.

CONTEXT: Conventional treatment of hypoparathyroidism is associated with decreased renal function and increased bone mineral density (BMD). OBJECTIVE: To evaluate the effects of 8 years of recombinant human parathyroid hormone (1-84) [rhPTH(1-84)] therapy on key biochemical and densitometric indices. DESIGN: Prospective open-label trial. SETTING: Tertiary medical center. PARTICIPANTS: Twenty-four subjects with hypoparathyroidism. INTERVENTION: Treatment with rhPTH(1-84) for 8 years. MAIN OUTCOME MEASURES: Supplemental calcium and vitamin D requirements, serum calcium and phosphorus levels, calcium-phosphate product, urinary calcium excretion, estimated glomerular filtration rate (eGFR) and BMD. RESULTS: PTH therapy was associated with progressive reduction in supplemental calcium (57%; P < 0.01) and active vitamin D (76%; P < 0.001) requirements over 8 years. Serum calcium concentration was stable; urinary calcium excretion declined 38% (P < 0.01). eGFR remained stable and was related to baseline eGFR and serum calcium levels. Calcium-phosphate product was below the recommended limit; serum phosphorus remained within normal range. Lumbar spine and total hip BMD increased, peaking at 4 (mean ± SE, 4.6% ± 1.5%; P = 0.01) and 8 years (2.6% ± 1.1%; P = 0.02), whereas femoral neck BMD did not change and one-third radius BMD decreased (mean ± SE, -3.5% ± 1.1%; P = 0.001). BMD at all sites was higher throughout the 8 years than in the age- and sex-matched reference population. Hypercalcemia and hypocalcemia were uncommon. CONCLUSION: rhPTH(1-84) is a safe and effective treatment for hypoparathyroidism for 8 years. Long-term reductions in supplemental requirements and biochemical improvements with stable renal function are maintained.

The Effects of Long-term Administration of rhPTH(1-84) in Hypoparathyroidism by Bone Histomorphometry.

Hypoparathyroidism is a rare disorder that is associated with abnormal bone properties. Recombinant human parathyroid hormone (1-84) [rhPTH(1-84)] in short-term studies has beneficial skeletal effects. Although rhPTH(1-84) will likely be used indefinitely, long-term effects on skeletal microstructure are unknown. We therefore studied histomorphometric changes with transiliac crest bone biopsies before and after 8.3 ± 1 years of rhPTH(1-84) in 13 hypoparathyroid subjects compared with 45 controls. Before institution of rhPTH(1-84), skeletal remodeling indices were markedly suppressed. With long-term treatment, indices of bone remodeling increased. Mineralizing surface increased by 26-fold (0.3 ± 1 to 7.9 ± 7%, p = 0.003), bone formation rate increased by 15-fold (0.003 ± 0.01 to 0.047 ± 0.05 µm2 /µm/day, p = 0.007), osteoid width doubled (1.9 ± 1 to 4.3 ± 1 lamellae, p = 0.017), and osteoid surface tripled (3.3 ± 3 to 10.8 ± 6%, p = 0.011). Bone resorption as measured by eroded surface increased (4.6 ± 2 to 7.5 ± 3%, p = 0.021). Structural changes demonstrated intratrabecular tunneling, with increases in cancellous bone volume (19.6 ± 5 to 29.1 ± 11%, p = 0.017) and trabecular number (1.8 ± 1 to 2.5 ± 1 #/mm, p = 0.025). Cortical porosity tended to increase (6.3 ± 5 to 9.5 ± 3%, p = 0.07). Mineralizing surface, osteoid surface, and eroded surface surpassed control levels, as did cancellous bone volume, trabecular number, and cortical porosity. These data, the first to reflect such long exposure of any PTH for any disease, illustrate that PTH establishes and maintains a new skeletal state for at least 8 years in hypoparathyroidism. © 2018 American Society for Bone and Mineral Research.