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.
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.


CONCLUSIONS
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.


BACKGROUND
Clinical trial registration number (EUDRACT2006-005532-24 & NCT00486369).
Karsdal
M A
MA
Nordic Bioscience A/S, Herlev, Herlev, Denmark. mk@nordicbioscience.com
Byrjalsen
I
I
Bay-Jensen
A C
AC
Henriksen
K
K
Riis
B J
BJ
Christiansen
C
C
D000284:Administration, Oral; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000652:urine; D015992:Body Mass Index; D015519:Bone Density / Q000187:drug effects / Q000235:genetics; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002116:Calcitonin / Q000008:administration & dosage* / Q000627:therapeutic use; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002940:Circadian Rhythm / Q000235:genetics; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D017063:Outcome Assessment, Health Care / Q000379:methods; D010919:Placebos; D011237:Predictive Value of Tests; D012474:Salmon; D012720:Severity of Illness Index; D012727:Sex Characteristics
D015415:Biomarkers; D010919:Placebos; C028815:salmon calcitonin; D002116:Calcitonin