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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.

Karsdal MA, Byrjalsen I, Bay-Jensen AC, Henriksen K, Riis BJ, Christiansen C - BMC Musculoskelet Disord (2010)

Bottom Line: 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).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.Bone resorption was higher in females than males, while cartilage degradation was correlated with increasing KL-score and only weakly associated with BMI.

View Article: PubMed Central - HTML - PubMed

Affiliation: Nordic Bioscience A/S, Herlev, Herlev, Denmark. mk@nordicbioscience.com

ABSTRACT

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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Time course during the day of concentrations serum CTX-I (filled circles) and urinary CTX-II (open circles) in A) untreated subjects and B) subjects treated with sCT. Values shown are concentrations relative to pre-dose at 08:00 and given as mean ± 1 SEM for serum CTX-I and geometric mean ± SEM for urinary CTX-II. A meal was given at 13.00 hours and a light meal at 15.30 as described in the material and methods. Dinner was served at 18.00. Modified from [46].
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Figure 5: Time course during the day of concentrations serum CTX-I (filled circles) and urinary CTX-II (open circles) in A) untreated subjects and B) subjects treated with sCT. Values shown are concentrations relative to pre-dose at 08:00 and given as mean ± 1 SEM for serum CTX-I and geometric mean ± SEM for urinary CTX-II. A meal was given at 13.00 hours and a light meal at 15.30 as described in the material and methods. Dinner was served at 18.00. Modified from [46].

Mentions: CTX-I displayed marked diurnal variation, in which a more than 50% decrease in levels was seen as a response to intake of lunch in the placebo group. CTX-II displayed lower levels of diurnal variation in the placebo group; however the kinetics of the changes were comparable to those in CTX-I (Figure 5A), indicating that CTX-II levels also are affected by the lunchtime meal. In the combined sCT treatment group analysis, robust reductions in both CTX-I and CTX-II were observed shortly after the morning dose, albeit with a more rapid reduction in CTX-I than CTX-II (Figure 5B). The marker levels remained suppressed throughout the day and early evening. The data are modified from [46].


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.

Karsdal MA, Byrjalsen I, Bay-Jensen AC, Henriksen K, Riis BJ, Christiansen C - BMC Musculoskelet Disord (2010)

Time course during the day of concentrations serum CTX-I (filled circles) and urinary CTX-II (open circles) in A) untreated subjects and B) subjects treated with sCT. Values shown are concentrations relative to pre-dose at 08:00 and given as mean ± 1 SEM for serum CTX-I and geometric mean ± SEM for urinary CTX-II. A meal was given at 13.00 hours and a light meal at 15.30 as described in the material and methods. Dinner was served at 18.00. Modified from [46].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2902412&req=5

Figure 5: Time course during the day of concentrations serum CTX-I (filled circles) and urinary CTX-II (open circles) in A) untreated subjects and B) subjects treated with sCT. Values shown are concentrations relative to pre-dose at 08:00 and given as mean ± 1 SEM for serum CTX-I and geometric mean ± SEM for urinary CTX-II. A meal was given at 13.00 hours and a light meal at 15.30 as described in the material and methods. Dinner was served at 18.00. Modified from [46].
Mentions: CTX-I displayed marked diurnal variation, in which a more than 50% decrease in levels was seen as a response to intake of lunch in the placebo group. CTX-II displayed lower levels of diurnal variation in the placebo group; however the kinetics of the changes were comparable to those in CTX-I (Figure 5A), indicating that CTX-II levels also are affected by the lunchtime meal. In the combined sCT treatment group analysis, robust reductions in both CTX-I and CTX-II were observed shortly after the morning dose, albeit with a more rapid reduction in CTX-I than CTX-II (Figure 5B). The marker levels remained suppressed throughout the day and early evening. The data are modified from [46].

Bottom Line: 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).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.Bone resorption was higher in females than males, while cartilage degradation was correlated with increasing KL-score and only weakly associated with BMI.

View Article: PubMed Central - HTML - PubMed

Affiliation: Nordic Bioscience A/S, Herlev, Herlev, Denmark. mk@nordicbioscience.com

ABSTRACT

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).

Show MeSH
Related in: MedlinePlus