Bone metabolism in ochronotic patients

Abstract

Abstract. Aliberti G, Pulignano I, Schiappoli A, Minisola S, Romagnoli E, Proietta M (Università di Roma 'La Sapienza', Rome, Italy). Bone metabolism in ochronotic patients (Case report). J Intern Med 2003; 254: 296-300.We investigated skeletal involvement in five male and two female patients with ochronosis, aged 26-82 years. The main parameters of mineral metabolism, together with biochemical markers of bone resorption (urinary N-telopeptides of type I collagen) and formation (serum bone isoenzyme of alkaline phosphatase and serum osteocalcin) were evaluated. In the same subjects lumbar spine and femoral bone mineral density (BMD) were also measured by dual energy X-ray absorptiometry. All patients but the younger 26-year-old patient had lower than normal bone mass at femoral neck and total hip, showing marked osteopenia in three cases and osteoporosis in the remaining three cases. However, at lumbar spine BMD measurement provided spuriously overestimated results, because of intervertebral disc calcification and osteophyte formation. As far as biochemical markers of bone turnover are concerned, the most relevant finding was the increased N-telopeptides of type I collagen urinary excretion. Our results suggest that ochronosis may be associated with increased bone resorption rate leading to an accelerated bone loss. A role of the homogentisic acid polymer deposit in bone matrix and cells, possibly with osteocyte damage and interference in collagen metabolism, might be hypothesized.

Alkaptonuric Ochronosis with Aortic Valve and Joint Replacements and Femoral Fracture: A Case Report and Literature Review

“…Moreover, in organ cultures of embryonic chick calvaria it was shown that homogentisic acid inhibits intracellular hydroxylysine formation diminishing intermolecular cross-links that are critically important for the structural function of the newly synthesized collagen. 39 It should be mentioned that in our patient, as in other reported cases, 38 while femoral neck bone mineral density was markedly reduced, the lumbar spine bone mineral density was normal or increased. This seeming paradox might be due to extensive intervertebral disc calcification.…”

“…37 In a series of ochronotic patients, the biochemical markers of bone turnover showed increased bone resorption (high urinary excretion of crosslinked N-telopeptides of type I collagen) with an almost normal bone formation in 6 out of 7 patients indicating accelerated bone loss. 38 Importantly, these changes were associated with reduced femoral bone mineral density. Moreover, in organ cultures of embryonic chick calvaria it was shown that homogentisic acid inhibits intracellular hydroxylysine formation diminishing intermolecular cross-links that are critically important for the structural function of the newly synthesized collagen.…”

The role of calcified cartilage and subchondral bone in the initiation and progression of ochronotic arthropathy in alkaptonuria

“…There is thinning and reduced mineralization of some underlying trabeculae and sclerotic changes in others similar to that previously reported in bone marrow lesions in OA (27–29). Although the aggressive resorption appears to be focal, it is noteworthy that enhanced urinary excretion of crosslinked N‐telopeptides of type I collagen has been reported in alkaptonuria patients (30).…”

A case of alkaptonuria – ultrasonographic findings

“…The ochronotic pigment was not found in osteoblasts, but in the cytoplasmic vacuoles of osteoclasts, osteocytes and calcified matrix [2]. However, while the bone formation markers are normal in AKU, the resorbtion markers (urinary secretion of crosslinked N -telopeptides of type 1 collagen) are elevated, thus leading to osteoporosis [9]. Vertebral and femoral fractures were described in AKU [2].…”