Daniel-Henri Manicourt

Effects of calcitonin on subchondral trabecular bone changes and on osteoarthritic cartilage lesions after acute anterior cruciate ligament deficiency.

Because SBM may contribute to cartilage breakdown in OA, experimental OA was induced in dogs by transecting the anterior cruciate ligament of the knee and treating with either CT or a placebo. CT significantly reduced both SBM and cartilage lesions. This study supports the use of CT in the treatment of canine experimental OA.

Urban Tropospheric Ozone Increases the Prevalence of Vitamin D Deficiency among Belgian Postmenopausal Women with Outdoor Activities during Summer.

CONTEXT By absorbing sunlight UVB and thereby reducing cutaneous vitamin D photosynthesis, ozone, a common urban pollutant, could cause hypovitaminosis D. OBJECTIVES The objective of the study was to establish the characteristics and percentage of subjects with serum 25-hydroxyvitamin D [25(OH)D] less than 75 nmol/liter among postmenopausal women engaging in outdoor activities in either Brussels or the countryside. DESIGN/SETTING This was a cross-sectional study conducted in a university research hospital. PATIENTS/METHODS Among 249 women consulting for either shoulder tendonitis or lumbar spine osteoarthritis, 121 free of conditions and drugs affecting bone and calcium metabolism completed two food-frequency questionnaires within 15 d and we selected the 85 subjects with retest scores within the +/- 15% of test scores. Other parameters included sun exposure index (SEI), PTH levels, and femoral neck T-score. RESULTS Urban residents (n = 38) and rural residents (n = 47) did not differ in mean ages, body mass indices, and vitamin D intakes. When compared with rural inhabitants, urban inhabitants were exposed to ozone levels 3 times higher, and despite a higher mean SEI (113 vs. 87; P < 0.001), they had a higher prevalence of 25(OH)D less than 75 nmol/liter (84 vs. 38%). After adjusting for SEI, 25(OH)D was 2-fold higher in rural residents, and after adjusting for 25(OH)D, SEI was 3-fold higher in urban residents. Femoral neck T-scores correlated positively with 25(OH)D and negatively with PTH levels. CONCLUSIONS Air pollution may be a neglected risk factor for hypovitaminosis D, which is known to compromise several health outcomes. As long as 25(OH)D is greater than 75 nmol/liter, calcium intakes greater than 17.5 mmol/d are unnecessary to prevent elevations in PTH levels.

Effects of diclofenac, aceclofenac and meloxicam on the metabolism of proteoglycans and hyaluronan in osteoarthritic human cartilage.

Since nonsteroidal anti‐inflammatory drugs (NSAIDs) may impair the ability of the chondrocyte to repair its damaged extracellular matrix, we explored the changes in the metabolism of newly synthesized proteoglycan and hyaluronan (HA) molecules produced by aceclofenac, diclofenac and meloxicam in human osteoarthritic (OA) cartilage. Explants were sampled from the medial femoral condyle and were classified by use of the Mankins histological‐histochemical grading system. Cartilage specimens exhibited moderate (M) OA in 20 subjects and had severe (S) OA in 20. Cartilage explants were pulsed with [‐3H]‐glucosamine and chased in the absence or in the presence of 0.3–3 μg ml−1 of either aceclofenac, diclofenac or meloxicam. After papain digestion, the labelled chondroitin sulphate ([‐3H]‐proteoglycans) and [‐3H]‐HA molecules present in the tissue and media were purified by anion‐exchange chromatography. In cartilage with MOA and SOA, the metabolic balance of proteoglycan and HA was unaffected by diclofenac. In contrast, and in a dose‐dependent manner, aceclofenac and meloxicam both increased the synthesis of proteoglycans and HA in explants with MOA and SOA; these two NSAIDs also reduced significantly the net loss of [‐3H]‐proteoglycans and [‐3H]‐HA molecules from cartilage explants. The data obtained in short‐term in vitro cultures indicate that, at the concentrations found in synovial fluid, aceclofenac and meloxicam may exert a favourable effect on the overall metabolism of proteoglycans and HA in cartilage with MOA and SOA.

Comparative Effect of Nimesulide and Ibuprofen on the Urinary Levels of Collagen Type II C-Telopeptide Degradation Products and on the Serum Levels of Hyaluronan and Matrix Metalloproteinases-3 and -13 in Patients with Flare-Up of Osteoarthritis

AbstractBackground and aim: Because in vitro studies have shown that nimesulide not only preferentially inhibits COX-2 but also reduces the action/release of pro-inflammatory cytokines, down-regulates the synthesis and/or activity of collagenase(s), and releases reactive oxygen species and other toxic substances from neutrophils, this study investigated whether nimesulide and ibuprofen could affect levels of biochemical markers of joint inflammation and collagen catabolism in patients with flare-up of knee or hip osteoarthritis. Methods: Ninety patients were included in this randomised, prospective, singleblind study. They received either nimesulide (n = 45) or ibuprofen (n = 45) for a 4-week treatment period. The following parameters were analysed by ELISA: urinary levels of C-terminal cross-linking telopeptide of type II collagen (CTX-II), a marker of type II collagen breakdown; serum levels of hyaluronan (HA), a marker of synovial inflammation and hyperplasia; and circulating levels of stromelysin-1 (matrix metalloproteinase-3 [MMP-3]), collagenase-1 (MMP-1) and collagenase-3 (MMP-13). Statistical analysis used was ANOVA. Results: At the end of the treatment period, nimesulide but not ibuprofen markedly reduced the urinary levels of CTX-II (p < 0.001) and the serum levels of HA (p < 0.05), two markers known to prognosticate poor outcome of the osteoarthritis disease process. Nimesulide also reduced the serum levels of both MMP-3 (p < 0.05) and MMP-13 (p < 0.001). Furthermore, in the nimesulide group, the decrease in levels of CTX-II correlated significantly with the decrease in levels of HA and MMP-13. Conclusion: Although nonsteroidal anti-inflammatory drugs are effective in improving pain and disability in OA patients, to date it has been unclear to what extent these drugs could affect joint metabolism and hence joint structure. Patients with flare-up of their osteoarthritis disease process exhibit enhanced levels of markers of joint inflammation and cartilage collagen breakdown, which were markedly decreased by nimesulide but not by ibuprofen.

Chondrocytes, synoviocytes and dermal fibroblasts all express PH-20, a hyaluronidase active at neutral pH

Hyaluronan (HA), an important component of connective tissues, is highly metabolically active, but the mechanisms involved in its catabolism are still largely unknown. We hypothesized that a protein similar to sperm PH-20, the only mammalian hyaluronidase known to be active at neutral pH, could be expressed in connective tissue cells. An mRNA transcript similar to that of PH-20 was found in chondrocytes, synoviocytes, and dermal fibroblasts, and its levels were enhanced upon stimulation with IL-1. In cell layers extracted with Triton X-100 – but not with octylglucoside – and in culture media, a polyclonal antipeptide anti-PH-20 antibody identified protein bands with a molecular weight similar to that of sperm PH-20 (60 to 65 kDa) and exhibiting a hyaluronidase activity at neutral pH. Further, upon stimulation with IL-1, the amounts of the neutral-active hyaluronidase increased in both cell layers and culture media. These findings contribute potential important new insights into the biology of connective tissues. It is likely that PH-20 facilitates cell-receptor-mediated uptake of HA, while overexpression or uncontrolled expression of the enzyme can cause great havoc to connective tissues: not only does HA fragmentation compromise the structural integrity of tissues, but also the HA fragments generated are highly angiogenic and are potent inducers of proinflammatory cytokines. On the other hand, the enzyme activity may account for the progressive depletion of HA seen in osteoarthritis cartilage, a depletion that is believed to play an important role in the apparent irreversibility of this disease process.

CHAPTER 25 – Products of Cartilage Metabolism

This chapter discusses the major products of articular cartilage metabolism with special emphasis on those that are relevant as body fluid markers. It provides a brief review of the structure–function relationships of the major matrix building blocks. The cartilage matrix contains several molecules that are found in much higher concentrations than in other tissues. The attention that aggrecan and collagen type II are currently receiving as potential markers of specific metabolic alterations in cartilage disease will likely extend to less abundant molecules found to play key roles in the maintenance of matrix homeostasis. As the understanding of the function and metabolism of these molecules improves, so will their potential as markers of the irreversible destabilization of the collagenous meshwork or of other specific alterations in cartilage matrix organization.

101 CALCITONIN PREVENTS THE LOSS OF CONNECTIVITY AND COMPLEXIITY OF TRABECULAR SUBCHONDRAL BONE IN EARLY STAGES OF CANINE OSTEOARTHRITIS

Figure 3 Conclusions: In normal human femoral condyles, the SBP is comprised of the condensation of approximately two horizontal trabeculae after which there are many communicating marrow spaces. This represents little or no barrier to the ingress of marrow constituents after a breach in the subchondral bone. In osteoarthritis the sclerotic SBP presents a substantial barrier to marrow stimulation procedures (data not shown). By contrast, all animals have subchondral bone plates that are thicker, more mineralized and have more bone volume compared to similar human tissue. Thus, these are not valid models of the normal human SBP, but instead could be considered an approximation of sclerotic human subchondral bone. These data explain why the response to injury or microfracture in large species such as the horse may underestimate human reparative capacity.