Bone mineral density in pseudohypoparathyroidism type 1a

Abstract

Context: The biochemical hallmark of pseudohypoparathyroidism type 1a (PHP1a) is resistance to PTH, but based on tissue-specific imprinting of GNAS, PTH resistance may be limited to the renal cortex. Some studies have shown that bone is responsive to PTH, suggesting that PHP1a patients with chronically elevated PTH levels may have low bone mineral density (BMD).

Setting: This observational study was conducted at the Institute of Clinical and Translational Research, Johns Hopkins Medical Institutions.

Subjects: Twenty-two children and adults with PHP1a were studied.

Main outcome measure: The main outcome measure was BMD Z-score at the lumbar spine (LS), total hip, femoral neck, and total body using dual-energy x-ray absorptiometry, relative to height, weight, and pubertal status.

Results: The mean (+/-SD) Z-score for height was 0.77 +/- 1.66 and 1.85 +/- 1.15 for BMI. The BMD Z-score at each of the four sites studied was as follows: LS, 0.29 +/- 1.08; total hip, 0.27 +/- 1.24; femoral neck, 0.02 +/- 1.26; and total body, 0.98 +/- 1.50. Only two subjects (9%) had BMD Z-scores less than -2, and each had additional risk factors for low BMD. BMD in total body and LS spine corrected for height-for-age Z-score was significantly greater than normal. There was no correlation between PTH level and BMD Z-score or between body mass index and BMD Z-score.

Conclusions: Despite secondary hyperparathyroidism, region-specific BMD is not reduced in patients with PHP1a, and total body BMD is significantly greater than normal.

Figures

Figure 1

Distribution of BMD Z-scores for LS (L1–L4), LS BMDhaz, and HAZ-adjusted TH, FN, and TB. The box-and-whisker plots indicate the minimum, 25th percentile, median, 75th percentile, and maximum observation for all BMD Z-scores.

Figure 2

Correlation between intact PTH levels and BMD Z-scores for LS (L1–L4), TH, FN, and TB. White circles indicate children (<18 yr old); black circles indicate adults (≥18 yr old). R2, Correlation coefficient, p, P value.

Figure 3

Correlation of BMI Z-score and BMD Z-scores for LS (L1–L4), TH, FN, and TB. White circles indicate children (<18 yr old); black circles indicate adults (≥18 yr old). R2, Correlation coefficient, p, P value.