Case Report: Stress Fractures in Systemic Lupus Erythematosus After Long-Term Methotrexate Use

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Researchers report the case of a 64-year-old woman with systemic lupus erythematosus and recurrent bilateral stress fractures of the calcaneus due to long-term methotrexate use.

A case report published in Lupus demonstrated the negative effect of long-term use of methotrexate (MTX) on bone density, resulting in peculiar stress fractures in a patient with systemic lupus erythematosus (SLE). The researchers noted that this was positively influenced by the termination of MTX treatment and the use of combination denosumab plus teriparatide therapy.

The investigators presented the case of a 64-year-old German woman with SLE who experienced recurrent bilateral stress fractures of the calcaneus resulting from long-term MTX use. Based on a detailed skeletal evaluation using dual-energy x-ray absorptiometry, her fractures were attributed to osteoporomalacia with pronounced trabecular thinning and increased bone resorption. Following years of unsuccessful treatment with bisphosphonates, combined denosumab plus teriparatide therapy was initiated, and belimumab was added to the treatment regimen in order to avoid the use of intermittent corticosteroid therapy. Following determination that these treatment measures were not associated with a significant improvement in the patient’s bone issues, MTX therapy was eventually discontinued.

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The cessation of MTX treatment was followed by rapid clinical improvement in the patient. In a follow-up magnetic resonance imaging scan performed after 18 months, the patient’s stress fractures had nearly disappeared.

Moreover, the patient’s bone density and microarchitecture were shown to have improved markedly. She was able to bear her full weight again, and the detected stress reactions in her bone were now shown to be only residual in nature.

According to the results of this case study analysis, the investigators proposed the rigorous screening of symptomatic patients with SLE who have undergone long-term MTX therapy to ascertain the presence of any stress fractures and osteoporosis, which will help provide the best medical care for such individuals. They recommend further exploration of the respective effects of MTX discontinuation and bone-specific therapies with respect to the healing of stress fractures in these patients.


Rolvien T, Creutzfeldt AM, Lohse AW, Amling M. Stress fractures in systemic lupus erythematosus after long-term MTX use successfully treated by MTX discontinuation and individualized bone-specific therapy [published online April 4, 2019]. Lupus. 961203319841434. doi:10.1177/0961203319841434