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.

Oral salmon calcitonin reduces Lequesne's algofunctional index scores and decreases urinary and serum levels of biomarkers of joint metabolism in knee osteoarthritis.

OBJECTIVE: To evaluate the effects of oral salmon calcitonin (sCT) on Lequesne's algofunctional index scores and on biomarkers of joint metabolism in knee osteoarthritis. METHODS: In this randomized, double-blind trial, patients received either placebo (n = 18), 0.5 mg of sCT (n = 17), or 1 mg of sCT (n = 18) daily for 84 days. Biomarkers included C-telopeptide of type II collagen (CTX-II), type II collagen neoepitope C2C, collagenases (matrix metalloproteinase 1 [MMP-1], MMP-8, and MMP-13), stromelysin (MMP-3), tissue inhibitors of metalloproteinases 1 and 2, and hyaluronan. Statistical analysis included nonparametric tests. RESULTS: A total of 41 patients completed the study (13 in the group receiving 0.5 mg of sCT and 14 in each of the other 2 other groups). Although, on day 84, patients in both the placebo group and the group receiving 1 mg of sCT exhibited a similar significant decrease in pain scores, a significant reduction in the function score was observed only in the 2 sCT groups. On day 84, there was no significant decrease in biomarker levels in the placebo group, whereas significant reductions in the levels of both MMP-3 and hyaluronan were observed in the 2 sCT groups. The group of patients receiving 1 mg of sCT exhibited significant decreases in the levels of CTX-II, C2C, and MMP-13. CONCLUSION: By improving functional disability and by reducing levels of biomarkers that are thought to be predictive of joint space narrowing (and thus cartilage loss), oral sCT at a dose of 1 mg might be a useful pharmacologic agent in human knee OA.

Inulin and fructo-oligosaccharides differ in their ability to enhance the density of cancellous and cortical bone in the axial and peripheral skeleton of growing rats.

Although dietary fructans improve calcium absorption and bone mineral content (BMC) in rats, their effect on calcium bioavailability and bone density may vary with their degree of polymerization. Therefore, for a 3-month period, growing rats received either a control diet or a diet enriched with either oligofructose (OLF) or inulin. At sacrifice, body weight, lean body mass and appendicular bone length were similar in the 3 groups. Rats fed fructans had a similar increase in cecal wall weight (30%), but the relative increase in cecal levels of calbinding-9 K was 2 in the OLF group and 4 in the inulin group. Further, the significant decrease in serum levels of type I collagen C-telopeptide was greater in the inulin group (30%) than in the OLF group (16%). The increase in whole-body bone mineral content (BMC) as measured by DXA was greater in the inulin group than in the OLF group but DXA detected an increase in the BMC of excised femurs only in the inulin group. In contrast, pQCT conducted ex vivo detected a significant increase in the area and mineral density (BMD) of the cancellous bone of both the proximal tibia and vertebra in rats fed fructans and the effect of inulin was greater (P < 0.01) than that of OLF (P < 0.05). Further, inulin but not OLF significantly enhanced the BMD of the cortical bone in both appendicular and peripheral sites (P < 0.01) as well as the polar stress/strain index of femurs (P < 0.01). These observations suggest that, although both inulin and OLF both have a positive effect on BMD, the greatest effect of inulin is related to the higher capacity of this fructan to reduce bone resorption. The different anti-resorptive capacity of the 2 fructans might be related to their different impact on calcium absorption and bioavailability since the increase in cecal amounts of calbindin-9 K, a protein known to play an important role in calcium absorption, was greater in rat fed inulin than in rats fed OLF. Although cecal wall hyperplasia may be of concern, it remains to establish whether the positive effect of fructans observed on calcium absorption in humans is also associated with a positive effect on bone mass and/or mineral density.

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.

BACKGROUND 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, single- blind 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.

Role of alendronate in therapy for posttraumatic complex regional pain syndrome type I of the lower extremity.

OBJECTIVE: To evaluate the effects of the antiresorptive agent alendronate at a daily oral dose of 40 mg in patients with posttraumatic complex regional pain syndrome type I (CRPS I) of the lower extremity. METHODS: Forty patients were enrolled in this 8-week randomized, double-blind, placebo-controlled study of alendronate therapy for CRPS I, a condition associated with regional osteoclastic overactivity. An optional 8-week open extension of alendronate therapy (weeks 12-20) was available after a 4-week period without therapy. Clinical assessments included joint mobility, edema of the lower extremity, tolerance to pressure in the lower extremity, and levels of spontaneous pain. Urinary levels of type I collagen N-telopeptide (NTX) were assessed by enzyme-linked immunosorbent assay. Patients were examined at weeks 4, 8, 12, 16, 20, and 24. Statistical analysis included two-way factorial analysis of variance. RESULTS: In contrast to placebo-treated patients (n = 20), all of the alendronate-treated patients (n = 19) exhibited a marked and sustained improvement in levels of spontaneous pain, pressure tolerance, and joint mobility, as well as a significant reduction in urinary levels of NTX at weeks 4 and 8. The improvement was maintained at week 12. Twelve patients from each treatment group volunteered for the 8-week open trial, and all of them had a positive response to alendronate. CONCLUSION: Our findings support the use of oral alendronate in posttraumatic CRPS I. By reducing local acceleration of bone remodeling, alendronate might relieve pain by effects on nociceptive primary afferents in bone, pain-associated changes in the spinal cord, and possibly also through a central mechanism.

Treatment with calcitonin prevents the net loss of collagen, hyaluronan and proteoglycan aggregates from cartilage in the early stages of canine experimental osteoarthritis.

OBJECTIVE: To evaluate the effect of calcitonin (CT) on the histology and biochemistry of articular cartilage from unstable operated and nonoperated knee in a canine model of experimental osteoarthritis (OA). METHODS: Eighteen dogs underwent anterior cruciate ligament transection (ACLT) of the right knee and were randomly distributed into three groups of six dogs each. From day-1 after surgery until sacrifice 84 days post-ACLT, each dog received a daily nasal spray that delivered the placebo, 100 units of CT or 400 units of CT. Histologic lesions were scored. Hyaluronan (HA) and antigenic keratan sulfate (AgKS) were quantified by enzyme-linked immunosorbent assays (ELISAs), whereas aggrecan molecules extracted under nondissociative conditions were characterized by velocity gradient centrifugation. RESULTS: All canine cruciate-deficient knees developed OA. At a daily dose of 400 units, CT had no effect on the size of osteophytes but significantly reduced the severity of cartilage histologic lesions in unstable knees. CT also enhanced the HA content as well as the size distribution and relative abundance of fast-sedimenting aggrecan aggregates in cartilage from both operated and nonoperated knees. On the other hand, in the CT-treated group, the cartilage content of AgKS increased in operated joints, but not in nonoperated joints. CONCLUSIONS: Because CT delivered as a nasal spray markedly reduced the severity of most OA changes, both at the histological and biochemical level, this form of therapy may have benefits for humans who have recently experienced a traumatic knee injury, and as well as for dogs who spontaneously rupture their ACL.

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

UNLABELLED: 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. INTRODUCTION: Because subchondral bone remodeling (SBM) may contribute to cartilage breakdown in osteoarthritis (OA), we evaluated to what extend calcitonin (CT) might affect cartilage and bone changes in the early stages of canine experimental OA. MATERIALS AND METHODS: Twelve dogs underwent transection of the anterior cruciate ligament (ACLT) of the right knee. After ACLT, each animal received a daily nasal spray delivering either 400 U of CT (CT-treated group; n = 6) or a placebo (PL-treated group; n = 6). At day 84 after surgery, animals were killed, and cartilage changes were graded. BMD and volume fraction (BVF) were assessed by pQCT in different regions of interest (ROIs) of the subchondral cancellous bone of tibial plateaus (TPs). Statistics included a 2 x 2 factorial analysis with +/-CT as one factor and +/-ACLT as the other. RESULTS AND CONCLUSIONS: Nonoperated (N-OP) knees were normal in both groups. In the PL-treated group, ACLT knees all exhibited OA changes, which predominated in the medial knee compartment. Furthermore, compared with N-OP knees, the BMD and BVF of ACLT joints were both markedly reduced in medial TP but not in lateral TP. In contrast, in the CT-treated group, cartilage OA lesions of ACLT knees were significantly reduced, and there was no difference in BMD and BFV between N-OP and ACLT knees. These findings suggest that the loss of subchondral trabeculae contributes to cartilage breakdown, possibly by enhancing cartilage deformation on joint loading. By counteracting bone loss, CT reduced cartilage OA lesions, and thus, might be useful in the treatment of OA in cruciate-deficient dogs.

Effect of nimesulide on the serum levels of hyaluronan and stromelysin-1 in patients with osteoarthritis: a pilot study.

This prospective preliminary single-blind study was conducted in patients suffering from osteoarthritis (OA) and requiring non-steroidal anti-inflammatory drugs (NSAIDs) to determine to what extent nimesulide (200 mg/day) and ibuprofen (1200 mg/day) could induce significant changes in the serum levels of matrix metalloproteinase-3 (MMP-3), tissue inhibitor-1 of MMPs (TIMP-1), hyaluronan (HA) and YKL-40 after a therapeutic time period of 28 days. The four biochemical parameters were assessed by using immunoassays. Nimesulide significantly reduced the serum levels of both HA and MMP-3, whereas ibuprofen increased moderately but significantly the serum concentrations of MMP-3 and had no effect on the serum concentrations of HA. The two NSAIDs were unable to change the serum levels of both TIMP-1 and YKL-40. These results suggest that nimesulide might have a favourable effect on the metabolism of OA joints.

Celecoxib has a positive effect on the overall metabolism of hyaluronan and proteoglycans in human osteoarthritic cartilage.

OBJECTIVE: To assess the effects of celecoxib, a cyclooxygenase (COX-2) selective inhibitor, on the metabolism of hyaluronan (HA) and proteoglycans (PG) in human cartilage explants with midrange severity of osteoarthritis (OA). Results were compared with those of diclofenac, a non-selective COX inhibitor. METHODS: Cartilage specimens (OA grade 4-8 on Mankin's scale) were pulsed with 3H -glucosamine and chased in the absence or presence of 1-10 micro g/ml of celecoxib or diclofenac. After papain digestion, the labeled chondroitin sulfate and HA molecules were purified by anion-exchange chromatography. RESULTS: Diclofenac did not affect the metabolic balance of PG and HA whereas, in a relatively dose-dependent manner, celecoxib increased the synthesis of HA and PG; celecoxib also reduced the net loss of labeled HA and PG molecules from cartilage explants. CONCLUSION: In short term in vitro cultures, celecoxib has a favorable effect on the overall metabolism of PG and HA. It is therefore unlikely that this drug would have a detrimental effect on articular cartilage during longterm administration. Further, celecoxib might help counteract the depletion of HA seen in OA cartilage.