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Effect of bisphosphonates on cartilage turnover assessed with a newly developed assay for collagen type II degradation products

H J Lehmann¹, U Mouritzen¹, S Christgau², P A C Cloos², C Christiansen¹

¹ Centre for Clinical and Basic Research, Ballerup, Denmark
² Osteometer Biotech A/S, Herlev, Denmark

Correspondence to:
Correspondence to:
Dr H J Lehmann, Centre for Clinical and Basic Research, Ballerup Byvej 222, 2750 Ballerup, Denmark;
hjl{at}ccbr.dk

Background: Animal studies of arthritis have suggested that bisphosphonates may have chondroprotective abilities.

Objective: To evaluate the effect of bisphosphonate treatment on cartilage degradation.

Methods: Type II collagen is almost exclusively localised in cartilage, where it is the major structural component of the tissue. Hence fragments derived from this protein should represent a specific index for cartilage degradation. The urinary concentration of collagen type II C-telopeptide degradation products (CTX-II) was measured by a new immunoassay (enzyme linked immunosorbent assay (ELISA)). The serum concentration of collagen type I C-telopeptide degradation products (CTX-I), a marker of bone degradation, was also measured by ELISA.

Participants: Two groups were studied. The alendronate group included 63 healthy postmenopausal women aged 45–54 randomly allocated to receive three years' treatment with 1 mg, 5 mg, 10 mg, or 20 mg alendronate daily or placebo. In the third year the women receiving 20 mg were switched to placebo. The ibandronate group included 119 women at least 10 years after the menopause aged <75 randomly allocated to receive 12 months' treatment with 0.25 mg, 0.5 mg, 1.0 mg, 2.5 mg, or 5 mg ibandronate daily or placebo followed by 12 months without treatment.

Results: 20 mg of alendronate and 2.5 and 5 mg of ibandronate treatment produced significant decreases in urinary CTX-II to about 50% of baseline. The level reached after three months of treatment remained practically constant during the following 12–36 treatment months. When treatment was withdrawn CTX-II values returned towards baseline. Serum CTX-I also decreased rapidly within three months, but to a level of about 30% of baseline.

Conclusions: The urinary excretion of CTX-II, a new marker of cartilage degradation, decreases significantly in response to bisphosphonate. This suggests that bisphosphonates may have chondroprotective effects in humans. By measurement of CTX-II it should be possible to monitor the effects of drugs that potentially inhibit cartilage destruction.

Keywords: collagen type II C-telopeptide; collagen; bisphosphonate treatment

Abbreviations: ANOVA, analysis of variance; BMD, bone mineral density; CTX-II (-I), collagen type II (I) degradation products; CV, coefficient of variation; ELISA, enzyme linked immunosorbent assay; mAb, monoclonal antibody; OA, osteoarthritis

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