Elcatonin in Combination with Risedronate Is More Effective than Risedronate Alone for Relieving Back Pain in Postmenopausal Women with Osteoporosis

Abstract

Intramuscularly administered elcatonin (ECT) reduces pain via the central nervous system. A prospective study was performed to determine whether ECT has a beneficial effect on back pain and function in postmenopausal women with osteoporosis during bisphosphonate therapy. Sixty-one postmenopausal osteoporotic women with back pain (mean age: 73.7 years, range: 54-96 years) were divided into two groups: the control group (n 30) and the ECT (intramuscular, 20 units a week) group (n 31). All patients received treatment with risedronate (17.5 mg weekly). The duration of the study was 8 weeks. Urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX), visual analogue scale (VAS) for back pain at rest and movement, and Roland-Morris Disability Questionnaire (RDQ) score for function were assessed. Urinary NTX levels, VAS at rest and movement, and RDQ score markedly decreased during 8 weeks of treatment in both ECT and control groups. A significant reduction in VAS at movement, but not in VAS at rest and RDQ score, was noted in the ECT group than in the control group. This effect was observed from 2 weeks after the start of therapy. These results suggested that ECT in combination with risedronate was more effective than risedronate alone for reducing back pain in postmenopausal women with osteoporosis.Key words elcatonin; risedronate; clinical vertebral fracture; postmenopausal woman; back pain Osteoporosis is commonly observed particularly in postmenopausal women, placing them at a significant risk of a fracture. Risedronate has been widely used as the first-line treatment for postmenopausal osteoporosis, because current evidence, based strictly on the principles of evidence-based medicine (EBM), suggests the efficacy of risedronate to reduce fracture incidence as well as its safety in postmenopausal women with osteoporosis.1-3) A recent systematic review analyzing 7 randomized controlled trials (RCTs) involving 14049 women confirms both clinically important and statistically significant reductions in vertebral, nonvertebral, and hip fractures after secondary prevention therapy. 4) It has been reported that the effect of risedronate to prevent clinical vertebral and nonvertebral fractures is recognized as early as 6 months after the start of treatment in postmenopausal women with osteoporosis.5,6) The anti-resorptive effects of nitrogen-containing bisphosphonates appear to result from their inhibition of an enzyme, farnesyl pyrophosphate synthase (FPPS), in osteoclasts.7) FPPS is a key enzyme in the mevalonate pathway, which generates isoprenoid lipids utilized for post-translational modification of small guanosine 5′-triphosphate (GTP)-binding proteins that are essential for osteoclast function. 7) One possible explanation for the early anti-fracture effect of risedronate is such inhibitory effect on FPPS in osteoclasts.Intramuscular treatment with elcatonin (ECT) is commonly used in Japan. ECT is a derivative of eel calcitonin synthesized by substituting an ethylene bond for its disulfide bond.8) ...

<p>Oxidative Stress Contributes to Hyperalgesia in Osteoporotic Mice</p>

“…29 However, postmenopausal osteoporotic patients with no fractures also suffer from chronic pain, which may be related to osteoclastic bone resorption. 30 Osteoclasts dissolve bone minerals by releasing protons through the a3 isoform of the vacuolar H + -ATPase (a3V-ATPase) and creating acidic microenvironments, which can activate the ASIC and TRP proteins. 31 Previous studies have demonstrated that the activation of ASIC3 and TRPV1 and the release of CGRP play important roles in acute inflammatory, chronic neuropathic and cancer pain.…”

Elcatonin attenuates disuse osteoporosis after fracture fixation of tubular bone in rats

“…For instance, Iwamoto et al presented data from a 5-year-period study demonstrating a sustainable role of ECT in post-menopausal women with osteoporosis [ 22 ]. In addition, another study in post-menopausal osteoporotic women confirmed the active effects of short-term combined treatment with bisphosphonate and ECT on lumbar BMD and bone turnover with back pain [ 23 , 24 ]. Furthermore, mild suppression of callus remodeling by ECT did not impair overall fracture healing process in the femoral fracture model of cynomolgus monkeys [ 9 ], whereas ECT facilitated osteoblast proliferation in the fracture site and suppressed the systemic acceleration of bone resorption without affecting cortical bone regeneration after drill-hole injuries in mice [ 10 ].…”

“…In addition, the concerns of anti-osteoporosis effects by ECT have been interpreted in the literatures [ 9 , 10 , 22 – 24 ]. For instance, Iwamoto et al presented data from a 5-year-period study demonstrating a sustainable role of ECT in post-menopausal women with osteoporosis [ 22 ].…”

Isopsoralen regulates PPAR‑γ/WNT to inhibit oxidative stress in osteoporosis

“…The number of patients presenting clinically with osteoporosis is increasingly common; a major hazard of osteoporosis is the associated increased risk of fracture and the potential induction of numerous other complications (2). It has been shown in epidemiological investigations that osteoporosis has become a common disease in clinics, and the importance of its associated risks has been increasingly recognized by clinicians (2,3).…”