Improving Bone Health in Patients With Rheumatoid Arthritis
Patients with rheumatoid arthritis (RA) are at an increased risk of bone loss due to RA-related systemic inflammation and glucocorticoid-induced osteoporosis. Improving bone health in patients with RA requires a comprehensive approach that includes—but is not limited to—corticosteroid dose reduction and/or discontinuation.
What is your approach to bone health and osteoporosis risk in patients with RA?
Professor of Medicine and Population and Quantitative Health Sciences
“Rheumatologists should attend to maintaining bone health in patients with RA.”
In RA, systemic inflammation is driven by a variety of cytokines, most prominently by proinflammatory cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF). Elevated TNF levels drive osteoclast maturation, which can result in both focal and generalized bone loss. TNF inhibition decreases bone loss but will not reverse or prevent it completely.
Interestingly, in a murine model of inflammatory arthritis, treatment with teriparatide in combination with a TNF inhibitor resulted in the repair of bone erosions. We investigated this treatment approach by randomizing patients with RA with bone erosions on hand radiographs and osteopenia, whose disease was controlled with a TNF inhibitor, to either teriparatide or no additional treatment for 1 year. However, although bone mineral density (BMD) improved, teriparatide had no effect on erosion volume.
In a post hoc analysis of the MONARCH trial, the effects of treatment on biomarkers relevant to bone remodeling were assessed. At week 24, biweekly dosing of sarilumab 200 mg was associated with higher concentrations of P1NP, a marker of osteoblast activation, compared with biweekly dosing of adalimumab 40 mg. Sarilumab treatment also resulted in significantly greater reductions in total RANKL, irrespective of corticosteroid use at baseline. Such findings suggest that IL-6 inhibition might have a greater effect on bone remodeling than TNF inhibition. However, these observations of the effect of targeted biologic treatment on biomarker concentrations must be confirmed by assessment of their effects on BMD.
Rheumatologists should attend to maintaining bone health in patients with RA, especially in postmenopausal women who have an additional risk for developing osteoporosis. Bone densitometry studies are appropriate to assess BMD, especially for those who are initiated on treatment with corticosteroids. In such patients, I obtain baseline bone densitometry studies and, if the patient has osteoporosis, I initiate treatment with a medication to inhibit bone resorption.
Other aspects of promoting bone health involve minimizing or avoiding the use of corticosteroids and, as alluded to earlier, initiating effective control of disease activity with conventional synthetic disease-modifying antirheumatic drugs such as methotrexate and targeted biologic agents (eg, anti-TNF or anti–IL-6 agents).
Professor of Medicine
“Any discussion of bone health should clearly involve the goal of corticosteroid dose reduction or discontinuation.”
At the earliest phases of osteopenia, many patients are reluctant to initiate antiresorptive therapy, even though they are clearly candidates for this type of treatment. It is very common for patients to be concerned about bisphosphonates and to raise safety issues about them. Thus, I think that it is important to share information and to have an informed discussion about antiresorptive therapy with our patients. Many patients have concerns about the development of bisphosphonate-induced spontaneous fractures and osteonecrosis of the jaw, so discussions should contextualize these potential adverse effects. One strategy is to frame the patient discussion such that the potential risks of these rare events are raised, but in the context of the much greater anticipated benefits in terms of overall reduction in the risk of fractures.
In addition, any discussion of bone health should clearly involve the goal of corticosteroid dose reduction or discontinuation. We know that even low doses of corticosteroids contribute to compromised bone health and that getting patients off of corticosteroids is still a tall, time-consuming task. It takes a lot of persistence on the part of the provider and the patient, and we just have not been doing a very good job with this.
Adjunct Clinical Professor, Division of Immunology/Rheumatology
“One of the problems with ensuring the successful management of osteopenia and osteoporosis in patients with RA is that there are not enough treatment options. Available osteoporosis therapies are not intended to be used indefinitely.”
One of the problems with ensuring the successful management of osteopenia and osteoporosis in patients with RA is that there are not enough treatment options. Available osteoporosis therapies are not intended to be used indefinitely. In particular, we have worried about what to do when patients have been on their bisphosphonate for 3 to 5 years. Bisphosphonates are not recommended to be used beyond this time frame because they are not building normal bone. Bisphosphonates are also difficult for many people to tolerate, and there are concerns about the risks of atypical femoral fractures and osteonecrosis of the jaw, even though the risk of these complications is quite low.
Zoledronic acid administered once per year for 3 years is a good alternative to oral agents. Denosumab administered every 6 months is another useful option and has benefits in terms of inhibiting progression of joint erosions in patients with RA, in addition to improving BMD. Teriparatide is also a very good agent, but unless somebody has had a fragility fracture and they are highly motivated, they will likely not want to take such a medication on a daily basis. We have used teriparatide for post-fracture healing, but we have had trouble getting patients to take it for longer than 3 or 6 months.
Adami G, Saag KG, Mudano AS, et al. Factors associated with the contemplative stage of readiness to initiate osteoporosis treatment. Osteoporos Int. 2020;31(7):1283-1290. doi:10.1007/s00198-020-05312-4
Adami G, Saag KG. Osteoporosis pathophysiology, epidemiology, and screening in rheumatoid arthritis. Curr Rheumatol Rep. 2019;21(7):34. doi:10.1007/s11926-019-0836-7
Burmester GR, Lin Y, Patel R, et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2017;76(5):840-847. doi:10.1136/annrheumdis-2016-210310
Chen J-F, Hsu C-Y, Yu S-F, et al. The impact of long-term biologics/target therapy on bone mineral density in rheumatoid arthritis: a propensity score-matched analysis. Rheumatology (Oxford). 2020;59(9):2471-2480. doi:10.1093/rheumatology/kez655
Dubrovsky AM, Lim MJ, Lane NE. Osteoporosis in rheumatic diseases: anti-rheumatic drugs and the skeleton. Calcif Tissue Int. 2018;102(5):607-618. doi:10.1007/s00223-018-0401-9
Gabay C, Burmester GR, Strand V, et al. Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomes. Arthritis Res Ther. 2020;22(1):70. doi:10.1186/s13075-020-02163-6
Khan AA, Morrison A, Hanley DA, et al; International Task Force on Osteonecrosis of the Jaw. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res. 2015;30(1):3-23. doi:10.1002/jbmr.2405
Solomon DH, Kay J, Duryea J, et al. Effects of teriparatide on joint erosions in rheumatoid arthritis: a randomized controlled trial. Arthritis Rheumatol. 2017;69(9):1741-1750. doi:10.1002/art.40156
Takeuchi T, Tanaka Y, Soen S, et al. Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): a randomised, double-blind, placebo-controlled phase 3 trial. Ann Rheum Dis. 2019;78(7):899-907. doi:10.1136/annrheumdis-2018-214827