Preventing and Treating Bone Loss in Lupus

October 4, 2016

Bone loss could affect as many as 31 percent of SLE patients. This article sums up the treatment options from first-line bisphosphonate recommendations to emerging treatments like abaloparatide.

Low bone density and subsequent factures from osteoporosis are persistent problems in patients with systemic lupus erythematosus (SLE). This has become especially true as improved treatments have expanded lifespans for these patients, enabling them to live to ages at which osteoporosis becomes higher-risk.

An article in the March issue of Current Treatment Options in Rheumatology outlines treatment options shown to boost bone mineral density, from first-line recommendations like bisphosphonates to emerging treatments like abaloparatide. The study, by Tracy Lin, M.D., and Jennifer Grossman, M.D., both of the University of California, Los Angeles, is featured in this article.

Treatment:  Lifestyle and Pharmaceutical

Lifestyle changes for patients with lupus are no different from lifestyle changes meant to prevent osteoporosis in healthy people. These include limiting alcohol use and smoking and maintaining a normal body weight. Exercise is known to have a protective effect in bone density, Drs. Lin and Grossman wrote.

Smoking is correlated with higher fracture risk and lower bone mineral density (BMD), but the data on alcohol is more mixed. Several studies have found no correlation between alcohol use and bone mineral density, while others have actually found higher BMD in patients with low or moderate alcohol risk. The American College of Rheumatology (ACR) 2010 guidelines for preventing osteoporosis and low BMD in systemic lupus erythematosus recommends reduced alcohol consumption.

Bisphosphonates are the first-line pharmaceutical prevention for bone loss in lupus. The ACR recommends alendronate, risedronate and zoledronic acid to prevent glucocorticoid-related osteoporosis. All have been shown to be efficacious by randomized clinical trials.

Another biphosphonate, ibandronate, can be administered either orally or intravenously and was shown in one trial to work better at increasing lumbar spine and femoral neck bone mineral density than alfacalcidol. Fracture reduction was not significantly different between the two treatments.

One drawback of bisphosphonates is their uncertain safety for patients of childbearing age. Because these drugs have a half-life of a decade or more in bone, bisphosphonates could potentially affect a woman's future pregnancies, even if the treatment were discontinued. Drs. Grossman and Lin recommend cautious use of bisphosphonates in premenopausal women, as well as a discussion of risk and benefit in this patient population.

Other pharmaceutical treatments are available. Calcium and vitamin D supplementation are a good option when dietary intake isn't sufficient. The ACR recommends doses of 800 to 1000 IU/day of vitamin D to achieve therapeutic levels. Calcium supplementation does have potential risks, as research has found a U-shaped relationship between calcium intake and cardiovascular mortality: High calcium intake has been linked with elevated risk of cardiovascular death.

Tariparatide, a recombinant human parathyroid hormone, is an option for high-risk patients with a 10-year risk of major osteoporotic fracture greater than 20 percent. One randomized clinical trial found that teriparatide outperformed alendronate on the outcomes of increased lumbar and hip BMD and lower fracture risk.

The antiresorptive peptide calcitonin has not been specifically studied in patients with SLE, but has been tested in patients taking glucocorticoids, with mixed results. Given the lack of consistent efficacy and the possibility of an increased risk of malignancy, calcitonin is not a first-line therapy for osteoporosis.

Hormonal therapies have been studied for the prevention of osteoporosis and bone loss in lupus patients, with some favorable results. Hormone replacement therapy, for example, led to an increase in lumbar spine BMD in SLE patients with ovarian failure. But, the authors of the article in Current Treatment Options in Rheumatologysaid that hormone therapies often increase the risk of stroke, cardiovascular events and blood clots, so hormone treatment options are not typically recommended for SLE patients.

Emerging Treatments

Abaloparatide, a parathyroid hormone-related protein analogue shown to increase lumbar spine and femoral neck bone mineral density as compared to teriparatide, is under study. Research thus far has been in healthy patients, but results suggest that abaloparatide is less likely to cause hypercalcemia than teriparatide.

A Phase III trial of the cathepsin K inhibitor odanacatib found a significant reduction in vertebral, hip and clinical non-vertebral fractures in odanacatib versus a placebo, as well as an increase in lumbar spine and total hip BMD. The results were published online in November 2014 in the journal Osteoporosis International. Phase II trials for two sclerostin inhibitors - romosozumab, blosozumab - showed increased bone mineral density at the lumbar spine, the total hip and the femoral neck. Phase II results for a sclerostin inhibitor, BPS804, have not yet been released.

Takeaways

Bisphosphonates are the frontline pharmaceutical option for the prevention and treatment of osteoporosis in systemic lupus erythematosus patients. Still, safety concerns can prevent this treatment of being useful for premenopausal women who might bear children in the future; bisphosphonates have also not been confirmed as a viable treatment option in the pediatric population.

Lifestyle considerations and calcium and vitamin D supplementation may be helpful for many systemic lupus erythematosus patients, with the caveat that overly high calcium intake may increase cardiac risk. Newer treatment options, such as tariparatide or denusumab, may be considered for high-risk patients when bisphosphonates don't work or aren't tolerated.

"Future therapies targeting different mechanisms within bone resorption and formation are currently under investigation and will significantly add to our limited armamentarium," Drs. Lin and Grossman wrote.

Prevalence and Causes of Bone Problems in Lupus

Though low bone mineral density is a well-known comorbidity in systemic lupus erythematosus, studies differ on the precise prevalence. Factors such as sample demographics, the site of measurement and precise cutoffs used can lead to varying estimates of low bone density in this population from 31.5 to 20 -26.1 percent.

Research on the reason for these bone problems is mixed, likely indicating multiple etiologies. One study found a correlation between bone loss and cumulative glucocorticoid dose, echoing similar findings in many studies. Disease activity itself plays a role, as several studies of patients never treated with glucocorticoids have found elevated risk of bone loss, Drs. Lin and Grossman wrote. In addition, vitamin D deficiency, age, sex, ethnicity and traditional risk factors for osteoporosis can explain some bone loss in lupus patients. The occurrence of symptomatic fractures increases five-fold in women with systemic lupus erythematosus.

 

References:

Lin T, Grossman J. Prevention and Treatment of Bone Disease in Systemic Lupus ErythematosusCurrent Treatment Options in Rheumatology Curr Treat Options in Rheum. 2016;2(1):21-35. DOI:10.1007/s40674-016-0034-y.

Mok C, Mak A, Ma K. Bone mineral density in postmenopausal Chinese patients with systemic lupus erythematosusLupus lupus. 2005;14(2):106-112. DOI:10.1191/0961203305lu2039oa.

Cramarossa G, Urowitz MB, Su J, Gladman D, Touma Z. Prevalence and associated factors of low bone mass in adults with systemic lupus erythematosusLupus. 2016. DOI:10.1177/0961203316664597.

Lane NE. Therapy Insight: osteoporosis and osteonecrosis in systemic lupus erythematosusNature Clinical Practice Rheumatology Nat Clin Pract Rheumatol. 2006;2(10):562-569. DOI:10.1038/ncprheum0298.

Bone HG, Dempster DW, Eisman JA, et al. Odanacatib for the treatment of postmenopausal osteoporosis: development history and design and participant characteristics of LOFT, the Long-Term Odanacatib Fracture TrialOsteoporosis International. 2015;26(2):699-712. DOI:10.1007/s00198-014-2944-6.