Bone Disease in Connective Tissue Disease/Systemic Lupus Erythematosus

Abstract

This article reviews recent advances in the research of the mechanisms of bone loss, as well as clinical features, economic impact and therapeutic implications of osteoporosis and fractures in patients with systemic lupus erythematosus (SLE) as an illustration of bone disease in a complex systemic autoimmune connective tissue disease. Recent studies demonstrated an increased incidence of osteoporosis and peripheral and vertebral fractures in patients with SLE. The aetiology of bone loss in SLE is multifactorial, including clinical osteoporosis risk factors, systemic inflammation, serological factors, metabolic factors, hormonal factors, possibly genetic factors and medication-induced adverse effects. The incidence of symptomatic fractures in patients with SLE is increased 1.2–4.7-fold and age, disease duration, glucocorticoid use, previous cyclophosphamide use, seizures and a prior cerebrovascular event have been identified as important risk factors. Moreover, a high prevalence of morphometric vertebral fractures was demonstrated, while one in three of these patients has normal bone density, which finding points to the multifactorial aetiology of fractures in SLE. The clinical consequences and economic burden of osteoporosis and fractures as glucocorticoid treatment-related adverse events and the high frequency of glucocorticoid therapy underline the importance of reducing glucocorticoid treatment and prescribing steroid-sparing agents. No data on fall risk and its determinants and the relationship with the occurrence of fractures in patients with SLE are currently available. Fall risk might be increased in lupus patients for several reasons. In addition, the recently reported high prevalence (20%) of frailty in SLE patients may contribute to the increased fracture incidence. Therefore, the relationships between fall risk, frailty and fracture occurrence in SLE might be interesting subjects for future studies.

Bone health, an often forgotten comorbidity in systemic lupus erythematosus: a comment on the new recommendations

“…Osteoporosis and fragility fractures occur frequently among SLE patients, being also present in juvenile SLE patients, men and premenopausal women, population groups usually at low risk. SLE is associated with an increased risk for osteoporosis and vertebral fractures, with a prevalence of morphometric vertebral fracture ranging from 14% to 50% in patients with a mean age around 40 2. In particular, a recent very large, population-based study on over 47 000 patients reported SLE to be associated to a twofold increased risk for fracture, threefold in case of lupus nephritis.…”

IL-33/IL-31 Axis in Osteoporosis

“…This dialogue, although still partially undeciphered, represents a promising research field, since its understanding could provide new insights for the design of targeted therapeutic strategies for osteoporosis [12]. Most of the pathologies causing osteoporosis are characterized by a chronic inflammatory background [13][14][15]. The menopausal estrogen decline and the aging process induce osteoporosis, mainly increasing the production of inflammatory cytokines that exert osteoclastogenic properties [9].…”

10 most important contemporary challenges in the management of SLE

“…Osteoporosis is a source of chronic pain and disability which contributes to morbidity and is a major challenge to the quality of life. SLE is significantly associated with lower bone mineral density (BMD) levels and with an increased fracture risk at all sites, especially vertebral fractures,35–37 which are often asymptomatic 35. The aetiology of bone loss and fractures is multifactorial in SLE, including GC therapy, disease activity, early menopause (such as in patients treated with intravenous cyclophosphamide), vitamin D deficiency (related to photoprotection) and frailty 35.…”

“…This should include an evaluation of dietary calcium intake, consumption of bone toxics (tobacco, alcohol and excess salt intake), a search for risk factors for fracture risk estimation (personal history of low trauma fracture) as well as a systematic measurement of BMD in all patients with SLE, including men and children aged 7+ 36. If BMD is abnormal, an X-ray examination of the dorsal and lumbar spine should be performed, searching for asymptomatic prevalent fractures 35. The detection of one or more asymptomatic prevalent vertebral fracture with at least osteopaenia is an indication for antiosteoporotic treatment.…”