Methotrexate osteopathy: five cases and systematic literature review

Robin, François; Cadiou, Simon; Albert, Jean-David; Bart, Géraldine; Coiffier, Guillaume; Guggenbuhl, Pascal

doi:10.1007/s00198-020-05664-x

Cited by 19 publications

(15 citation statements)

References 33 publications

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“…The precise mechanism of MTX action in RA is not known ( 58 ), but demonstrated clinical efficacy makes MTX the number one choice of therapy in good responders. Its effect on bone homeostasis at low-dose treatment as in RA is also unclear, while, with dose increment, there is a risk of MTX osteopathy ( 59 ). Despite intervention, some patients fail to respond to medication, and even minimally active disease promotes further local and systemic bone loss ( 60 , 61 ).…”

Section: Discussionmentioning

confidence: 99%

Preventive CCL2/CCR2 Axis Blockade Suppresses Osteoclast Activity in a Mouse Model of Rheumatoid Arthritis by Reducing Homing of CCR2hi Osteoclast Progenitors to the Affected Bone

et al. 2021

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Detailed characterization of medullary and extramedullary reservoirs of osteoclast progenitors (OCPs) is required to understand the pathophysiology of increased periarticular and systemic bone resorption in arthritis. In this study, we focused on identifying the OCP population specifically induced by arthritis and the role of circulatory OCPs in inflammatory bone loss. In addition, we determined the relevant chemokine axis responsible for their migration, and targeted the attraction signal to reduce bone resorption in murine collagen-induced arthritis (CIA). OCPs were expanded in periarticular as well as circulatory compartment of arthritic mice, particularly the CCR2hi subset. This subset demonstrated enhanced osteoclastogenic activity in arthritis, whereas its migratory potential was susceptible to CCR2 blockade in vitro. Intravascular compartment of the periarticular area contained increased frequency of OCPs with the ability to home to the arthritic bone, as demonstrated in vivo by intravascular staining and adoptive transfer of splenic LysMcre/Ai9 tdTomato-expressing cells. Simultaneously, CCL2 levels were increased locally and systemically in arthritic mice. Mouse cohorts were treated with the small-molecule inhibitor (SMI) of CCR2 alone or in combination with methotrexate (MTX). Preventive CCR2/CCL2 axis blockade in vivo reduced bone resorption and OCP frequency, whereas combining with MTX treatment also decreased disease clinical score, number of active osteoclasts, and OCP differentiation potential. In conclusion, our study characterized the functional properties of two distinct OCP subsets in CIA, based on their CCR2 expression levels, implying that the CCR2hi circulatory-like subset is specifically induced by arthritis. Signaling through the CCL2/CCR2 axis contributes to OCP homing in the inflamed joints and to their increased osteoclastogenic potential. Therefore, addition of CCL2/CCR2 blockade early in the course of arthritis is a promising approach to reduce bone pathology.

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Section: Discussionmentioning

confidence: 99%

Preventive CCL2/CCR2 Axis Blockade Suppresses Osteoclast Activity in a Mouse Model of Rheumatoid Arthritis by Reducing Homing of CCR2hi Osteoclast Progenitors to the Affected Bone

et al. 2021

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“…Cyclosporine and tacrolimus are also associated with bone loss, while azathioprine and mycophenolic acid are not ( 20 ). Methotrexate is only very rarely associated with osteopathy, mainly at excessive doses or due to drug interactions ( 77 ). While the mammalian target of rapamycin (mTOR) pathway plays an important role in bone metabolism, the clinical effects of mTOR inhibitors on osteoporosis or fracture risk remain poorly understood ( 20 ).…”

Section: Resultsmentioning

confidence: 99%

Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club

et al. 2022

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Glucocorticoids are effective immunomodulatory drugs used for many inflammatory disorders as well as in transplant recipients. However, both iatrogenic and endogenous glucocorticoid excess are also associated with several side effects including an increased risk of osteoporosis and fractures. Glucocorticoid-induced osteoporosis (GIOP) is a common secondary cause of osteoporosis in adults. Despite availability of clear evidence and international guidelines for the prevention of GIOP, a large treatment gap remains. In this narrative review, the Belgian Bone Club (BBC) updates its 2006 consensus recommendations for the prevention and treatment of GIOP in adults. The pathophysiology of GIOP is multifactorial. The BBC strongly advises non-pharmacological measures including physical exercise, smoking cessation and avoidance of alcohol abuse in all adults at risk for osteoporosis. Glucocorticoids are associated with impaired intestinal calcium absorption; the BBC therefore strongly recommend sufficient calcium intake and avoidance of vitamin D deficiency. We recommend assessment of fracture risk, taking age, sex, menopausal status, prior fractures, glucocorticoid dose, other clinical risk factors and bone mineral density into account. Placebo-controlled randomized controlled trials have demonstrated the efficacy of alendronate, risedronate, zoledronate, denosumab and teriparatide in GIOP. We suggest monitoring by dual-energy X-ray absorptiometry (DXA) and vertebral fracture identification one year after glucocorticoid initiation. The trabecular bone score might be considered during DXA monitoring. Extended femur scans might be considered at the time of DXA imaging in glucocorticoid users on long-term (≥ 3 years) antiresorptive therapy. Bone turnover markers may be considered for monitoring treatment with anti-resorptive or osteoanabolic drugs in GIOP. Although the pathophysiology of solid organ and hematopoietic stem cell transplantation-induced osteoporosis extends beyond GIOP alone, the BBC recommends similar evaluation, prevention, treatment and follow-up principles in these patients. Efforts to close the treatment gap in GIOP and implement available effective fracture prevention strategies into clinical practice in primary, secondary and tertiary care are urgently needed.

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“…MTX is postulated to affect osteoblastic activity and may enhance osteoclastic bone resorption. Prolonged usage of MTX can result in MTX osteopathy, which was defined by a clinical triad: pain, osteoporosis, and stress fractures [25] . In addition, application of glucocorticoids (GC) is the most frequent cause of osteoporosis provoked by medicaments.…”

Section: Discussionmentioning

confidence: 99%

Stress fracture of proximal tibia after proximal fibula osteotomy: A case report

Wang

Huang

Pei

2021

International Journal of Surgery Case Reports

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Introduction Proximal fibula osteotomy (PFO) is a new method for treating medial compartment osteoarthritis of the knee, which is based on the theory of differential settlement (nonuniform settlement). This procedure has been widely recognized for its advantages of relative simplicity, low rate of postoperative complications, and low postoperative costs. Stress fracture of the proximal tibia after PFO has not been previously reported. Case presentation We report a 62-year-old woman with chronic rheumatoid arthritis (RA) underwent left PFO for chronic knee pain, who developed a stress fracture of the proximal tibia more than 1 year after PFO. Clinical discussion In the early stage of proximal tibia stress fracture, due to the concealment of radiography manifestations, doctors from another hospital performed total knee arthroplasty (TKA) for the patient. They ignored the treatment of stress fracture of the proximal tibia, and the stress fracture was further aggravated after surgery. Six months later, the patient underwent open reduction and internal fixation with a plate and screw in the left proximal tibia fracture at our hospital. The patient was followed up at the hospital three months after open reduction, and the proximal tibia stress fracture began to heal. Conclusion RA is usually not confined to the medial compartment and its pathogenesis is different from that of osteoarthritis. Therefore, PFO is not an appropriate procedure for this type of patient.

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Methotrexate osteopathy: five cases and systematic literature review

Abstract: Methotrexate osteopathy. Five cases and systematic literature review.

Cited by 19 publications

References 33 publications

Preventive CCL2/CCR2 Axis Blockade Suppresses Osteoclast Activity in a Mouse Model of Rheumatoid Arthritis by Reducing Homing of CCR2hi Osteoclast Progenitors to the Affected Bone

Preventive CCL2/CCR2 Axis Blockade Suppresses Osteoclast Activity in a Mouse Model of Rheumatoid Arthritis by Reducing Homing of CCR2hi Osteoclast Progenitors to the Affected Bone

Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club

Stress fracture of proximal tibia after proximal fibula osteotomy: A case report

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