Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2011 Feb;164(2):295-301.
doi: 10.1530/EJE-10-0795. Epub 2010 Nov 9.

Osteosclerosis in two brothers with autosomal dominant pseudohypoparathyroidism type 1b: bone histomorphometric analysis

Anne Marie Sbrocchi  1 , Frank Rauch, Margaret L Lawson, Stasia Hadjiyannakis, Sarah Lawrence, Murat Bastepe, Harald Jüppner, Leanne Marie Ward
Affiliations
Case Reports

Osteosclerosis in two brothers with autosomal dominant pseudohypoparathyroidism type 1b: bone histomorphometric analysis

Anne Marie Sbrocchi et al. Eur J Endocrinol. 2011 Feb.

Abstract

Objective: Pseudohypoparathyroidism (PHP) is a heterogeneous disorder characterized by hypocalcemia and hyperphosphatemia resulting from selective renal resistance to parathyroid hormone (PTH). One autosomal dominant form of PHP type 1b (PHP-Ib) is most frequently caused by a maternally inherited 3-kb deletion within STX16, the gene encoding syntaxin 16. To date, increased bone mineral density (BMD) has been described only in PHP type 1a, and there is a lack of detailed information on bone histomorphometry in PHP-Ib. The objective of this report was to present trans-iliac static and dynamic histomorphometry in two brothers with the 3-kb deletion in the STX16 region and elevated BMD.

Design: Observational study of two brothers (age 18.0 and 22.7 years) with the 3-kb STX16 deletion and increased BMD.

Results: The brothers had elevated PTH (146 pg/ml (15.6 pmol/l) and 102 pg/ml (10.9 pmol/l); normal: 10-64 pg/ml (1.1-6.8 pmol/l)) and striking osteosclerosis (lumbar spine areal BMD Z-scores: +5.4 and +4.9). Bone histomorphometry showed marked elevations in cortical width for both brothers (241 and 209% of the mean result expected for age), with elevations in the bone formation rate on the endocortical (119 and 260% of the healthy mean) and trabecular (220 and 190% of mean) surfaces.

Conclusion: Our findings suggest that PTH in this PHP-Ib genotype can increase cortical thickness due to its anabolic effect on endocortical bone, and underscore the heterogeneity in the skeletal phenotype among patients with PHP-Ib.

PubMed Disclaimer

Conflict of interest statement

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Figures

Figure 1
Figure 1
(A) Iliac bone sample from proband 1. Cortical width is 2429 µm. (B) Sample from proband 2. Cortical width is 2106 µm. Note the difference in their cortical width when compared to the control (mean value based on the healthy average = 1006 µm) (C).
See this image and copyright information in PMC

References

    1. Bastepe M. The GNAS locus and pseudohypoparathyroidism. Advances in Experimental Medicine and Biology. 2008;626:27–40. - PubMed
    1. Linglart A, Bastepe M, Jüppner H. Similar clinical and laboratory findings in patients with symptomatic autosomal dominant and sporadic pseudohypoparathyroidism type Ib despite different epigenetic changes at the GNAS locus. Clinical Endocrinology. 2007;67:822–831. - PubMed
    1. Kidd GS, Schaaf M, Adler RA, Lassman MN, Wray HL. Skeletal responsiveness in pseudohypoparathyroidism. A spectrum of clinical disease. American Journal of Medicine. 1980;68:772–781. - PubMed
    1. Murray TM, Rao LG, Wong MM, Waddell JP, McBroom R, Tam CS, Rosen F, Levine MA. Pseudohypoparathyroidism with osteitis fibrosa cystica: direct demonstration of skeletal responsiveness to parathyroid hormone in cells cultured from bone. Journal of Bone and Mineral Research. 1993;8:83–91. - PubMed
    1. Burnstein MI, Kottamasu SR, Pettifor JM, Sochett E, Ellis BI, Frame B. Metabolic bone disease in pseudohypoparathyroidism: radiologic features. Radiology. 1985;155:351–356. - PubMed

Publication types