Bone-related outcomes in patients with bullous pemphigoid: a population-based study

Bullous pemphigoid (BP) has been increasingly associated with systemic complications. Osteoporosis and femoral head fractures (FHF) are major public health concerns in aging populations, yet their potential link to BP remains underexplored. To evaluate the risk of osteoporosis and FHF in patients with BP and to assess the influence of different treatment regimens on these musculoskeletal outcomes. In this retrospective cohort study using the Clalit Health Services database in Israel, we analyzed 3924 patients with newly diagnosed BP and 19,280 matched controls. Incidence rates and hazard ratios (HRs) for osteoporosis and FHF were calculated using multivariate Cox regression, adjusting for demographic and clinical confounders. We further evaluated the impact of treatment strategies, including systemic corticosteroids (SCS), topical corticosteroids (TCS), and adjuvant immunosuppressants, on outcome risk. BP was associated with a significantly increased risk of osteoporosis (adjusted HR 1.66; 95% CI 1.40–1.96) and FHF (adjusted HR 1.23; 95% CI 1.03–1.47) compared to controls. Treatment with SCS significantly elevated osteoporosis risk relative to TCS (HR 1.59; 95% CI 1.00–2.56), while SCS monotherapy was associated with a lower risk of osteoporosis relative to SCS plus adjuvant immunosuppressants (HR 0.38; 95% CI 0.22–0.65). FHF was not significantly influenced by treatment modality but was a significant determinant of elevated mortality (HR 1.42; 95% CI 1.25–1.59). BP is independently associated with higher risks of osteoporosis and FHF. Use of SCS, especially in combination with immunosuppressants, predisposes BP patients to osteoporosis. These findings highlight the need for proactive bone health surveillance and fracture prevention in patients with BP, particularly those undergoing SCS.