Greater periosteal bone formation around the cortical bone area and other bone structure findings were observed among patients with primary hypertrophic osteoarthropathy (PHO), according to study results published in Journal of Bone Mineral Research.

Primary hypertrophic osteoarthropathy is a rare inherited disorder characterized by cutaneous and orthopedic symptoms, including pachydermia, digital clubbing, arthropathy, and periosteosis. Periosteosis is the hallmark of PHO and refers to the abnormal pathologic woven bone formation beneath the cortical bone of the long bones, which may result in long bone deterioration. However, data regarding bone changes in long bones of patients with PHO have not been well-detailed in the literature.

Researchers noted previous studies demonstrating an increased level of calcitonin gene-related peptide (CGRP), which has been associated with bone formation and inhibition of osteoclast remodeling. In addition, PHO has also been associated with an increase in prostaglandin E2 (PGE2) catabolizing enzyme and other bone resorption biomarkers.


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To evaluate bone microarchitecture and bone strength in PHO, researchers used high-resolution peripheral quantitative computed tomography (HR-pQCT).

Researchers noted that women were less likely to be affected by PHO and displayed atypical skeletal symptoms as seen in previous studies; thus, they were excluded from the analysis. Other exclusion criteria included use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), the bisphosphonates teriparatide, denosumab, hormonal therapy, and thyroxine, in the past year.

Overall, 20 men of Chinese Han ethnicity with PHO and 20 healthy participants were included in the study. All participants were age- and sex-matched. A total of 168 images from HR-pQCT were reviewed for the nondominant tibia. Additional biomarkers including urinary PGE2, serum phosphatase (ALP), beta-C-telopeptides of type I collagen (β-CTX), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), osteoprotegerin (OPG), and CGRP were measured to evaluate bone metabolism.

Compared with healthy control participants, patients with PHO had larger bone cross-sectional areas; lower total, trabecular, and cortical volumetric bone mineral density (vBMD); and compromising bone microstructures with more porous cortices, thinned trabeculae, reduced trabecular connectivity, and significantly more resorption of rod-like trabeculae at the distal tibia. Researchers noted that patients with PHO had bone microstructure and strength differences in long bones due to their generalized periosteosis condition. The HR-pQCT measurement showed increased cortical bone area and perimeters but decreased cortical vBMD in patients with PHO.

Researchers also noted that CGRP levels were significantly higher in patients with PHO (P <.05), suggesting that CGRP may be involved in periosteal formation and progression of PHO. Bone resorption biomarkers β-CTX, urinary PGEs, and sRANKL/OPG ratio were significantly increased in patients with PHO (P <.01). However, the bone formation marker ALP was similar among patients with PHO and healthy participants.

As study limitations, the researchers noted that HR-pQCT scans were of the load-bearing not the none-load bearing distal radius, which is less confounded by daily walking or loading. Spiculated periosteosis and trabecularization of the cortical bone in patients with PHO may have affected the evaluation of HR-pQCT images. Researchers also mentioned that the biomarkers used in the study may have been indicative of systemic or local bone turnover features in patients with PHO. Finally, histopathology analysis at a cellular level may have needed a biopsy that was not ethically feasible for the study.

“…further studies at bone tissue and cellular levels are desired to elaborate the cellular and molecular mechanisms underlying periosteosis and its pathology of PHO as well as development of targeted and effective therapy,” the researchers recommended.

Reference

Pang Q, Xu Y, Huang L, et al. Bone geometry, density, microstructure and biomechanical properties in the distal tibia in patients with primary hypertrophic osteoarthropathy assessed by second-generation HR-pQCT. J Bone Miner Res. Published online December 10, 2021. doi:10.1002/jbmr.4488

This article originally appeared on Rheumatology Advisor