Serum sclerostin level in premenopausal women with rheumatoid arthritis: relation to disease activity, fracture risk and bone mineral density

Abstract

Background
Rheumatoid arthritis (RA) is associated with increased risk of fractures due to decreased bone mass. Sclerostin is a glycoprotein that suppresses bone formation. It is expressed in osteocytes and some chondrocytes and works by suppressing osteoblast activity. This study aimed to assess the relation between serum sclerostin and rheumatoid disease activity, bone mineral density (BMD) and subsequently fracture risk.


Patients and methods
This case-control study included 50 premenopausal RA female (aged 18–50 years), and 50 healthy controls (aged, sex matched). Serum sclerostin level was assessed for all participants. Disease activity score (DAS28), BMD and fracture risk assessment tool (FRAX) were assessed for RA patients.


Results

RA patients showed higher levels of serum sclerostin compared to healthy controls, with mean (6.63 ± 4.60 vs. 4.62 ± 2.09 ng/mL,
p
 = 0.047). Serum sclerostin was not correlated with DAS28. There was a negative correlation between serum sclerostin and radius T-score (
r
 = − 0.298,
p
 = 0.036), and Z-score (
r
= -0.278,
p
 = 0.049). No correlations were found between serum sclerostin and femoral neck BMD, lumbar spine (T- and Z-scores), or major osteoporotic or hip fracture scores. DAS28 was negatively correlated with radius T-score (
r
 = − 0.295,
p
 = 0.038) and radius Z-score (
r
 = − 0.340,
p
 = 0.016). FRAX scores (major osteoporotic fracture and hip fracture) were positively correlated with age (
r
 = 0.646 and 0.397, respectively; both
p
 < 0.01) disease duration (
r
 = 0.480 and 0.426 respectively; both
p
 < 0.01), in addition to the duration of steroid therapy, particularly the duration of the minimum dose (
r
 = 0.357 and 0.460,
p
 = 0.011 and 0.001 for major osteoporotic and hip fracture, respectively), and with the duration of the maximum dose for hip fracture (
r
 = 0.300,
p
 = 0.034).



Conclusion
Serum sclerostin level is elevated in women with RA compared to healthy controls and is related to reduced peripheral BMD. Progressive disease factors such as longer disease duration, older age and higher disease activity, may contribute to worsening bone health and increased risk of hip and major osteoporotic fractures. Additionally, prolonged corticosteroid therapy may further exacerbate fracture risk. Overall, these findings highlight that BMD declines with advancing RA duration and activity, underscoring the importance of monitoring both disease progression and treatment exposures to mitigate fracture risk. Tight control of disease activity in RA patients is essential, as it may help preserve BMD and reduce the risk of OP. The use of steroids should be carefully limited to the lowest effective dose and shortest possible duration, particularly in patients at high risk of bone loss.