Osteoporosis in patients with rheumatoid arthritis: trends in the German National Database 2007–2017

Abstract

Osteoporosis is a frequent comorbidity in rheumatoid arthritis (RA). Due to the improved treatment options for RA, we expect a long-term decrease in osteoporosis as an accompanying disease. Data from the German National Database (NDB) were used to investigate whether the frequency of osteoporosis has changed in the last 10 years. From 2007 to 2017, approximately 4000 patients were documented annually with data on therapy and comorbidity. The cross-sectional data were summarised descriptively. Age, sex, disease duration, disease activity and glucocorticoids were considered as influencing factors. The Cochrane-Armitage test for trend was used to test whether the frequency of osteoporosis at the first visit changed from 2007 to 2017. Osteoporosis frequency in RA patients (mean age 63 years, 75% female) decreased from 20% in 2007 to 6% in 2017 (p < 0.001). The decrease affected women (22% to 17%) and men (14% to 8%) in all age groups and both short-term (≤ 2-year disease duration: 9% to 3%) and long-term RA patients (> 10-year disease duration: 28% to 20%). Patients with high disease activity and patients who took glucocorticoids (GC) were more often affected by osteoporosis than patients in remission or without GC. Drug prophylaxis in patients without osteoporosis increased (20% to 41% without GC, 48% to 55% with GC). Men with GC received less prophylactic treatment than women (48% vs. 57% in 2017). In this cohort, osteoporosis in patients with RA is less frequently observed compared to former years. RA-specific risk factors for osteoporosis such as disease activity and GC therapy have declined but long-term GC use is still present. Assessment of osteoporosis in RA patients should be investigated more consistently by bone density measurement. Male RA patients still need to be given greater consideration regarding osteoporosis drug prophylaxis, especially when GC therapy is needed.

Osteoporosis in Rheumatoid Arthritis: Dangerous Liaisons

“…Furthermore, previous studies have described that the risk of fracture in the next 10 years measured by FRAX is increased in ACPA positive patients (17). By contrast, recent publications show that patients achieving early RA remission have a similar OP risk profile than the general population (15).…”

“…Other biological agents such as tocilizumab, rituximab, and abatacept have shown a significant decrease in bone resorption markers and RANKL expression, which provides evidence of a beneficial effect on bone remodeling process slowing down bone loss (15). In a study, a 2-year treatment with tocilizumab showed improvement in BMD and significantly decreased levels of β-CTX in ACPA positive patients (97).…”

“…OP and RA share some common risk factors such as female gender (female: male ratio in RA: 3-4:1) and smoking. Other general OP risk factors such as age, low body mass index (BMI), menopause, diabetes or thyroid disorders (6,(13)(14)(15) are equally applicable to patients with RA and to the general population.…”

“…Other risk factors that can account for OP in RA include systemic inflammation associated with disease activity, local effect of immune cells leading to bone erosions, glucocorticoid (GC) therapy and impairment of physical activity (14). Therefore, OP and fractures are more frequent in patients with high disease activity (according to DAS28), presence of periarticular bone erosions and cumulative structural damage, RA disease duration ≥ 10 years, high HAQ score or high titers of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) positivity (6,9,10,(14)(15)(16). In one study, vertebral fracture risk in RA patients was related to longer disease duration, dose and duration Abbreviations: ACPA, anti-citrullinated protein antibodies; ACR, American College of Rheumatology; Anti-CarPA, anti-carbamylated protein antibodies; BMD, bone mineral density; BMI, body mass index; CI, confidence interval; CTX-I, carboxy-terminal telopeptide of type 1 collagen; CXCL8, C-X-C motif chemokine ligand 8; DAS28, disease activity score counted over 28 joints; DDK-1, Dickkopf-1 protein; DMARD(s), disease modifying anti-rheumatic drug(s); DXA, dual X-ray densitometry; DXR, dual X-ray radiogrammetry; EULAR, European league against Rheumatism; FRAX, fracture risk assessment tool; GC(s), glucocorticoid(s); HAQ, health assessment questionnaire; hTNF-tg, human tumor necrosis factor transgenic; Ig, immunoglobulins; IL, interleukin; IFN-, interferon gamma; M-CSF, macrophage colony-stimulating factor; OP, osteoporosis; OPG, osteoprotegerin; PEARL, Princesa early arthritis register longitudinal; PINP, procollagen type 1 N-terminal propeptide; RA, rheumatoid arthritis; RANK/RANK-L, receptor activator of nuclear factor (NF)-kB (RANK) and its ligand; RF, rheumatoid factor; TNF-α, tumor necrosis factor; TNFi, TNF-α inhibitors; Th, T helper lymphocytes; Treg, regulatory T cells; uNTx, cross-linked N-telopeptide of type I collagen; Wnt, drosophila segment polarity gene wingless and integrated or int-1 of the vertebrate homolog.…”

“…Interestingly, a decrease in the prevalence of OP and fractures has been described in the last 10 years, likely due to improved therapeutic options that have allowed rheumatologists to lead more RA patients to remission (15).…”