Clinical, biochemical, and radiographic effects of aminohydroxypropylidene bisphosphonate treatment in rheumatoid arthritis.

Abstract

SUMMARY A placebo controlled, double blind study of aminohydroxypropylidene bisphosphonate (APD), given by monthly intravenous infusion, was conducted in 40 patients with rheumatoid arthritis. Biochemical markers of increased bone resorption, such as fasting urinary calcium/ creatinine ratio and hydroxyproline/creatinine ratio, were suppressed significantly in the APD group to approximately 50% and 60% of the pretreatment level respectively, and serum calcium fell transiently after the first APD infusion. There was no significant effect on disease activity in either the APD or placebo groups as judged by clinical (grip strength, morning stiffness, visual analogue score) or laboratory (haemoglobin, platelet count, erythrocyte sedimentation rate, C reactive protein) criteria. An exception was the articular index which improved to a similar degree in both groups, falling from (mean (SEM)) 13X8 (1X8) to 7-2 (2-2) in the APD group and from 13-7 (1-9) to 6-8 (1.5) in the placebo group. Radiological progression occurred to a similar degree in both groups as assessed by the Sharp index (mean (SEM) 86 (13-1) v 95 (12-9)-APD group; 103 (15-1) v 110 (15-8)-placebo group), but there was no significant change in the Larsen index in either group (mean (SEM) 53 (4-2) v 57 (3.8)-APD; 62 (5-8) v 63 (5-6)-placebo). The lack of effect on radiological progression in the APD group indicates that focal erosive disease may either have progressed as the result of a non-osteoclast related mechanism, or that the intensity of bone resorption was too great to be inhibited by the doses of APD used. The biochemical response to APD presumably reflected inhibition of bone resorption at other sites, suggesting that further studies of the effects of bisphosphates on periarticular and systemic osteoporosis in rheumatoid arthritis may be of interest.

Contrast between effects of aminobisphosphonates and non‐aminobisphosphonates on collagen‐induced arthritis in mice

“…Therefore, the contrast between the sup- AA, adjuvant-induced arthritis; CA, collagen-induced arthritis; RA, rheumatoid arthritis; E, effective; NE, not effective; W, worsening. References: (1) Francis et al, 1972;(2) Flora, 1979;(3) Babier et al, 1986;(4) Francis et al, 1989;(5) Nugent et al, 1993;(6) Dunn et al, 1993a;(7) Markusse et al, 1990;(8) Ralston et al, 1989;(9) Tan et al, 1989;(10) Bijvoet et al, 1980;(11) Maccagno et al, 1994; (12) present results. pressive effect of non-aminoBPs and the ineffectiveness of aminoBPs on arthritis cannot be attributable to effects on bone resorption.…”

“…Ralston et al (1989) and Tan et al (1989) have found that it is not effective in restricting the progression of periarticular bone erosion, although the bone resorption was suppressed. These results seem to be in agreement with those of our animal experiments.…”

“…It is of considerable interest why such bone destruction occurs, even where there is a strong inhibition of physiological bone resorption in the growth plate. Ralston et al (1989) discussed the possibility that cells other than osteoclasts might be involved in the erosion of the bone in rheumatoid arthritis. We suggest that macrophages and/or granulocytes, in addition to their inflammatory roles in soft tissues, may also have a role in the destruction of bone.…”

Bisphosphonates: Environmental protection for the joint?

“…Numerous trials in patients with RA have demonstrated the beneficial effects of oral or parental bisphosphonates in preventing the progression of generalized skeletal bone loss and stabilizing systemic bone mass. Despite their success in preventing systemic bone loss, however, trials with bisphosphonates in patients with RA have not demonstrated efficacy with respect to attenuating the progression of focal bone erosions (6)(7)(8)(9)(10). In contrast, results of studies in several different animal models of inflammatory arthritis indicate that bisphosphonate treatment can produce beneficial effects in both systemic bone loss and progression of focal bone erosions (3,(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

Regulation of bone destruction in rheumatoid arthritis through RANKL-RANK pathways

“…Jarette et al [37] reported preliminary evidence that treatment with zoledronic acid plus methotrexate showed better results in reducing bone destruction than methotrexate alone. However, many other studies have failed to show positive effects of bisphosphonates against bone destruction in RA [38][39][40] . This may be because, in these studies, the treatment was initiated too late or the strength of the bisphosphonates used was not enough to treat the bone destruction in RA.…”