A morphological study of bone and articular cartilage in ochronosis

Abstract

An ochronotic femoral head has been studied morphologically under the light and the electron microscope. Its articular cartilage showed the alterations already reported in the literature, mainly consisting of erosions of the surface, pigment accumulation in chondrocytes and intercellular matrix, chondrocyte degeneration, the formation of pigmented, calcified and uncalcified microshards, and the presence of granulation tissue with macrophagic cells. The changes in bone were less severe than those in cartilage. Pigment was present in the calcified matrix. This did not seem to disturb the organization of the bone tissue, although it was diffusely osteoporotic, perhaps because of limb disuse. The preservation of calcified matrix might depend on the fact that its collagen fibrils are encrusted by mineral substance, which avoids the dangerous effects that the deposition of ochronotic pigment induces in the fibrils of soft connective tissues. On the other hand, the newly formed osteoid matrix remains uncalcified for too short a time to be modified by the pigment. Diffuse or granular pigmentation was found in a few osteocytes, while several of them were condensed or reduced to cellular fragments. Bone resorption often occurred near these osteocytes. However, this did not seem to alter the degree of bone remodelling, possibly because of the relatively low numbers of degenerated or dead osteocytes. Pigment was also contained in the cytoplasmic vacuoles of otherwise active osteoclasts, whereas it was not found in osteoblasts. On the whole, ochronosis in bone seems to induce the same changes as in other connective tissues. However, their severity appears to be limited by calcification, which prevents modifications in collagen fibrils, and by bone remodelling, which to some extent eliminates the oldest, pigment-richest parts of the tissue.

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

“…In an ochronotic femoral head, the pigment was not found in osteoblasts but was present in the calcified matrix as well as in the cytoplasmic vacuoles of osteoclasts and in osteocytes, some of which were degenerate or dead. 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.…”

“…6 In ochronosis, the changes in the bone are thought to be less severe than those in cartilage. 37 The accumulation of oxidized and polymerized products of homogentisic acid reduces the cross-linkage of collagen fibers leading to connective tissue failure, cartilage erosion, and progressive degenerative changes. 23 Although ochronosis in bone induces the same changes as in other connective tissues, the severity appears to be limited by calcification and bone remodelling.…”

“…23 Although ochronosis in bone induces the same changes as in other connective tissues, the severity appears to be limited by calcification and bone remodelling. 37 It is suggested that the detrimental effects of ochronotic pigment on the fibrils of soft connective tissues are avoided by the collagen fibrils of the bones because they are encrusted by a mineral substance and because the newly formed osteoid matrix remains uncalcified for too short of a time to be modified by the pigment. In an ochronotic femoral head, the pigment was not found in osteoblasts but was present in the calcified matrix as well as in the cytoplasmic vacuoles of osteoclasts and in osteocytes, some of which were degenerate or dead.…”

Ochronosis masquerading as pigmented villonodular synovitis: a case report

“…It gets deposited in the joint cartilage, intervertebral disc and collagen. Its destructive effects in cartilage and connective tissue may be related to increased cross-linkage of collagen [7,8].…”

“…The patient generally presents in the 3rd decade of life with degenerative arthritis and the diagnosis is suspected based on pigmentation of the ear cartilage and urine turning black on standing [1][2][3][4][5][6][7][8][9]. Ochronosis masquerading as pigmented villonodular synovitis is extremely rare.…”