Comparison of bone microstructure and strength in the distal radius and tibia between the different types of primary hypertrophic osteoarthropathy: an HR-pQCT study.

Primary hypertrophic osteoarthropathy (PHO) is a hereditary bone disease that is grouped into PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2) due to different causative genes. Data comparing bone microstructure between the two subtypes are scarce. This is the first study to find that PHOAR1 patients had inferior bone microstructure compared with PHOAR2 patients. PURPOSE: The primary goal of this study was to assess bone microarchitecture and strength in PHOAR1 and PHOAR2 patients and to compare them with age- and sex-matched healthy controls (HCs). The secondary goal was to assess the differences between PHOAR1 and PHOAR2 patients. METHODS: Twenty-seven male Chinese PHO patients (PHOAR1 = 7; PHOAR2 = 20) were recruited from Peking Union Medical College Hospital. The areal bone mineral density (aBMD) was assessed by dual-energy X-ray absorptiometry (DXA). Peripheral bone microarchitecture at the distal radius and tibia were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Biochemical markers of PGE2, bone turnover, and Dickkopf-1 (DKK1) were investigated. RESULTS: Compared with HCs, PHOAR1 and PHOAR2 patients had distinctively larger bone geometry, substantially lower vBMD at the radius and tibia, and compromised cortical microstructure at the radius. For trabecular bone, PHOAR1 and PHOAR2 patients showed different changes at the tibia. PHOAR1 patients had significant deficits in the trabecular compartment, resulting in lower estimated bone strength. Conversely, PHOAR2 patients showed a higher trabecular number, narrower trabecular separation, and lower trabecular network inhomogeneity than HCs, translating into preserved or slightly high estimated bone strength. CONCLUSION: PHOAR1 patients had inferior bone microstructure and strength compared with PHOAR2 patients and HCs. Additionally, this study was the first to find differences in the bone microstructure between PHOAR1 and PHOAR2 patients.

Two novel mutations in the SLCO2A1 gene in a Chinese patient with primary hypertrophic osteoarthropathy.

Primary hypertrophic osteoarthropathy (PHO) is a rare monogenetic disease characterized by digital clubbing, periostosis and pachydermia. Mutations in the 15-hydroxy-prostaglandin dehydrogenase (HPGD) gene and solute carrier organic anion transporter family member 2A1 (SLCO2A1) gene have been shown to be associated with PHO. Here, we described clinical characteristics in a Chinese patient with PHO, and identified two novel mutations in SLCO2A1: a heterozygous guanine-to-thymidine transition at the invariant -1 position of the acceptor site of intron 2 (c.235-1G>T) and a heterozygous missense mutation p.Pro219Leu (c.656C>T) in exon 5.