Oral salmon calcitonin reduces Lequesne's algofunctional index scores and decreases urinary and serum levels of biomarkers of joint metabolism in knee osteoarthritis

Abstract

Objective. To evaluate the effects of oral salmon calcitonin (sCT) on Lequesne's algofunctional index scores and on biomarkers of joint metabolism in knee osteoarthritis.Methods. In this randomized, double-blind trial, patients received either placebo (n ‫؍‬ 18), 0.5 mg of sCT (n ‫؍‬ 17), or 1 mg of sCT (n ‫؍‬ 18) daily for 84 days. Results. A total of 41 patients completed the study (13 in the group receiving 0.5 mg of sCT and 14 in each of the other 2 other groups). Although, on day 84, patients in both the placebo group and the group receiving 1 mg of sCT exhibited a similar significant decrease in pain scores, a significant reduction in the function score was observed only in the 2 sCT groups. On day 84, there was no significant decrease in biomarker levels in the placebo group, whereas significant reductions in the levels of both MMP-3 and hyaluronan were observed in the 2 sCT groups. The group of patients receiving 1 mg of sCT exhibited significant decreases in the levels of CTX-II, C2C, and MMP-13.Conclusion. By improving functional disability and by reducing levels of biomarkers that are thought to be predictive of joint space narrowing (and thus cartilage loss), oral sCT at a dose of 1 mg might be a useful pharmacologic agent in human knee OA.In vitro and in vivo studies (for review, see ref. 1) suggest that calcitonin (CT) might be a potential therapeutic agent in the setting of osteoarthritis (OA). Indeed, besides its analgesic and antiinflammatory properties, the hormone significantly counteracts subchondral bone changes, markedly reduces the progression of cartilage damage, and prevents the net loss of collagen, hyaluronan, and proteoglycan aggregates in a canine cruciate-deficiency model of OA. Because longterm administration of nasal and parenteral salmon CT (sCT) is hampered by the occurrence of local irritation, an oral formulation of sCT has been developed; the oral formulation is safe, well-tolerated, and produces a reproducible and dose-dependent inhibition of bone resorption (2).We therefore decided to conduct a preliminary phase IIa, randomized, placebo-controlled, doubleblind, parallel trial to assess the efficacy of oral sCT in knee OA. Lequesne's algofunctional index (3) was used to evaluate pain and functional disability. Furthermore, because up to 50% of placebo-treated patients in OA clinical trials might exhibit improvement of joint symptoms (4), we also quantified validated and/or purported biomarkers of OA progression and cartilage loss. These Supported by an institutional grant from Novartis AG to the

Can biochemical markers serve as surrogates for imaging in knee osteoarthritis?

“…A few of these studies have also investigated the radiographic severity of OA and serum or urinary biochemical markers (18)(19)(20)(21)(22)(23). In the present study, we analyzed the largest panel of biochemical markers ever investigated in a wellcharacterized cohort of patients with knee OA and we observed that 14 of them were significantly associated with at least 1 imaging feature.…”

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

“…Studies in the ACL dog model [144,145] also showed that subcutaneous injections of calcitonin under therapeutic conditions reduced the progression of OA cartilage and subchondral bone changes as well as the level of serum markers of bone resorption up to 4 months after the surgery. A small phase II trial assessing the efficacy of oral salmon calcitonin in knee OA was recently published [146]. Results showed an improvement in function scores as well as a reduction in some biomarker levels.…”

The chemical biomarkers C2C, Coll2‐1, and Coll2‐1NO2 provide complementary information on type II collagen catabolism in healthy and osteoarthritic mice

“…The serum levels of C2C/Cpropeptide of type II collagen, which indicate the ratio of type II collagen degradation to synthesis, are also elevated in OA-susceptible compared with OA-resistant guinea pigs (24). In humans, calcitonin has been shown to reduce the serum levels of C2C and alleviate OA symptoms (25). Furthermore, positive correlations have been found between the MRI T2 parameter and serum levels of C2C in OA knees (26).…”