Biochemical markers identify influences on bone and cartilage degradation in
osteoarthritis--the effect of sex, Kellgren-Lawrence (KL) score, body mass index
(BMI), oral salmon calcitonin (sCT) treatment and diurnal variation.
Author(s): Karsdal MA, Byrjalsen I, Bay-Jensen AC, Henriksen K, Riis BJ, Christiansen C.
Affiliation(s): Nordic Bioscience A/S, Herlev, Herlev, Denmark. mk@nordicbioscience.com
Publication date & source: 2010, BMC Musculoskelet Disord. , 11:125
BACKGROUND: Osteoarthritis (OA) involves changes in both bone and cartilage.
These processes might be associated under some circumstances. This study
investigated correlations between bone and cartilage degradation in patients with
OA as a function of sex, Kellgren-Lawrence (KL) score, Body Mass Index (BMI),
oral salmon calcitonin (sCT) treatment and diurnal variation.
METHODS: This study was a 2-week, double-blind, double-dummy, randomized study
including 37 postmenopausal women and 36 men, aged 57-75 years, with painful knee
OA, and a KL-score of I - III. Subjects were allocated to one of three treatment
arms: 0.6 mg or 0.8 mg oral sCT, or placebo given twice-daily for 14 days.
Correlations between gender, KL score, or BMI and the bone resorption marker,
serum C-terminal telopeptide of collagen type I (CTX-I), or the cartilage
degradation marker, urine C-terminal telopeptide of collagen type II (CTX-II)
were investigated.
RESULTS: At baseline, biomarkers indicated women with OA experienced higher bone
and cartilage degradation than men. CTX-I levels were significantly higher, and
CTX-II levels only marginally higher, in women than in men (p = 0.04 and p =
0.06, respectively). Increasing KL score was not correlated with bone resorption,
but was significantly associated with the cartilage degradation CTX-II marker in
both men and women (p = 0.007). BMI was significantly and negatively correlated
to the bone resorption marker CTX-I, r = -0.40 (p = 0.002), but showed only a
borderline positive correlation to CTX-II, r = 0.25 (p = 0.12). Before morning
treatments on days 1 and 14, no correlation was seen between CTX-I and CTX-II in
either the sCT or placebo group. However, oral sCT and food intake induced a
clear correlation between these bone and cartilage degradation markers. Four
hours after the first sCT dose on treatment days 1 and 14, a significant
correlation (r = 0.71, p < 0.001) between changes in both CTX-I and CTX-II was
seen. In the placebo group a weakly significant correlation between changes in
both markers was found on day 1 (r = 0.49, p = 0.02), but not on day 14.
CONCLUSION: Bone resorption was higher in females than males, while cartilage
degradation was correlated with increasing KL-score and only weakly associated
with BMI. Bone and cartilage degradation were not correlated in untreated
individuals, but dosing with oral sCT with or without food, and a mid-day meal,
decreased bone and cartilage degradation and induced a correlation between both
markers. Changes in bone and cartilage markers may aid in the identification of
potential new treatment opportunities for OA.
TRIAL REGISTRATION: Clinical trial registration number (EUDRACT2006-005532-24 &
NCT00486369).
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