IDS Bone and Cartilage Newsletter – April 2009

Welcome to the March issue of the IDS Bone and Cartilage Research Newsletter. Our aim is to provide you monthly updates on the latest findings in Bone and Cartilage research and welcome your feedback and input for future issues. We hope you find these of interest and please feel free to distribute a copy to your colleagues and fellow researchers.

Tibolone: uncoupling of bone and cartilage effects?

Osteoarthritis (OA) is the most common joint disease and a major cause of disability in people over 50 years of age. One hallmark of the disease is progressive degeneration of articular cartilage, generation of osteophytes and subsequent joint space narrowing. In clinical settings a number of studies have provided evidence for the coupling between bone and cartilage degradation. A selective estrogen-receptor modulator (SERM) was shown to protect against both bone and cartilage degradation (1). In another study cartilage degradation was found to be significantly lower in women using hormone replacement therapy (HRT) compared to controls (2, 1) and the cartilage degradation was significantly higher in postmenopausal women when compared to an age-matched group of pre-menopausal women (2).

In a recent study Karsdal et al (3) investigated whether Tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic properties, would have similar dual actions on both bone and cartilage turnover, as reported previously with SERMS and HRT.

Ninety-one healthy postmenopausal women aged 52-75 yrs entered a 2-yr double blind, randomized, placecbo controlled study of treatment with either 1.25 mg/day (n=36), or 2.5 mg/day tibolone (n=35), or placebo (n=20) as previously described (4). Second void morning urine samples were collected at baseline, and at 3, 6, 12, and 24 months. Urine CrossLaps® (CTX-I) ** and Urine CartiLaps® ELISA (CTX-II) was investigated as markers of bone resorption and cartilage degradation, respectively (both IDS Ltd).

Figure 1: Bone resorption. Urinary CTX-I
Tibolone inhibited bone resorption highly significantly with a plateau after 6 months (fig 1).

Figure 1: Bone resorption. Urinary CTX-I during 2 years of therapy in the groups receiving 2.5 mg, 1.25 mg of tibolone, or placebo. Values shown are geometric mean±1 SEM.

Tibolone did not affect cartilage degradation (fig 2). The observed effect of 2.5 mg of Tibolone was an increase of 19% [95% confidence interval -17%; +70%] in CTX-II.

Figure 2: Cartilage degradation. Urinary CTX-II during 2 years therapy in the groups receiving 2.5 mg, 1.25 mg of tibolone, or placebo. Values shown are geometric mean ±1 SEM.

Figure 2: Cartilage degradation. Urinary CTX-II
Collectively, the data suggests that bone resorption can be strongly attenuated without the secondary positive effects on cartilage degradation. These findings indicate effects on the uncoupling of the bone and cartilage from the synthetic steroid, Tibolone. These are in contrast to those observed with SERMs and HRT on both bone and cartilage degradation and may in part be described by the complicated pharmacology of Tibolone on testosterone, estrogen and progesterone receptors.

References

1. Christgau S, Tanko LB, Cloos PA, Mouritzen U, Christiansen C, Delaisse JM et al. Suppression of elevated cartilage turnover in postmenopausal women and in ovariectomized rats by estrogen and in a selective estrogen-receptor modulator (SERM). Menopause 2004, 11: 508-51
2. Mouritzen U, Christgau S, Lehmann HJ, Tanko LB, Christiansen C: Cartilage turnover assessed with a newly developed assay measuring collagen type II degradation products: influence of age, sex, menopause, hormone replacement therapy, and body mass index. Ann Rheum Dis 2003, 62: 332-336
3. Karsdal MA, Byrjalsen I, Leeming DJ, Christiansen C: Tibolone inhibits bone reosprion without secondary positive effects on cartilage degradation. BMC Musculoskelet Disord 2008, 9: 15
4. Bjarnason NH, Bjarnason K, Haarbo J, Rosenquist C, Christiansen C: Tibolone: prevention of bone loss in late postmenopausal women. J CLin Endocrinol Metab 1996, 81: 2419-2422