# Histomorphometric bone analysis in premenopausal women with longstanding rheumatoid arthritis and osteoporosis

**Authors:** Mariana O Perez, Lucas P Sales, Vanda Jorgetti, Valeria F Caparbo, Luciene M dos Reis, Ana C Medeiros-Ribeiro, Karina R Bonfiglioli, Andrea Y Shimabuco, Vinícius F Plantz, Camille P Figueiredo, Rosa M R Pereira, Eduardo F Borba, Diogo S Domiciano

PMC · DOI: 10.1093/jbmrpl/ziag012 · 2026-03-09

## TL;DR

This study examines bone health in premenopausal women with rheumatoid arthritis and osteoporosis, finding that bone fragility is due to structural and mineralization issues rather than typical osteoporosis.

## Contribution

The study provides novel histomorphometric insights into bone fragility in premenopausal rheumatoid arthritis patients, distinguishing it from classic osteoporosis.

## Key findings

- Premenopausal RA patients showed reduced trabecular thickness and increased cortical porosity.
- Mineralization kinetics were disturbed, with lower mineralizing surface and variable mineralization lag time.
- Osteoid indices correlated with disease activity, and mineralizing surface inversely with glucocorticoid dose.

## Abstract

Data on bone microarchitecture in premenopausal women with RA are scarce and have not been evaluated using histomorphometry. We assessed bone fragility in premenopausal RA women through static and dynamic histomorphometric parameters, compared to age- and sex-matched controls. Eighty patients were screened, and iliac crest biopsies were performed in those with fragility fractures or low BMD (Z-score ≤ −2.0). All analyses focus exclusively on the 12 women who underwent bone biopsy. Among these 12 premenopausal women with longstanding RA, mean age was 41.8 ± 6.6 yr and disease duration was 10.8 ± 5.8 yr. Bone volume (BV/TV) was numerically lower in RA patients compared with controls (p = .064). Thus, a reduction in bone volume cannot be excluded, given the limited statistical power. RA patients demonstrated reduced trabecular thickness, increased cortical porosity, and higher osteoclastic surface. Dynamic evaluation showed markedly lower mineralizing surface (MS/BS) and greater variability in mineralization lag time (Mlt). However, Mlt values remained within the physiological range and do not meet histological criteria for osteomalacia. Four patients (33%) showed absent tetracycline labeling. Osteoid indices correlated positively with disease activity, and MS/BS correlated inversely with glucocorticoid dose. In this selected group of premenopausal women with longstanding RA and osteoporosis by clinical criteria, bone fragility appears to result from a combination of trabecular thinning, cortical porosity, and disturbances in mineralization kinetics rather than from classic histomorphometric osteoporosis or osteomalacia.

Graphical Abstract

## Linked entities

- **Diseases:** rheumatoid arthritis (MONDO:0008383), osteoporosis (MONDO:0005298)

## Full-text entities

- **Genes:** CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, COL1A2 (collagen type I alpha 2 chain) [NCBI Gene 1278] {aka EDSARTH2, EDSCV, OI4}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, CYP27A1 (cytochrome P450 family 27 subfamily A member 1) [NCBI Gene 1593] {aka CP27, CTX, CYP27}, TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600] {aka CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** hepatitis C (MESH:D019698), RF (MESH:C538347), ) and C virus (MESH:D006526), Vertebral fractures (MESH:C535781), bone fragility (MESH:C536063), osteoporosis (MESH:D010024), thoracic fracture (MESH:D013896), anti-citrullinated protein (MESH:C536207), Inflammation (MESH:D007249), RA (MESH:D001172), fracture (MESH:D050723), osteomalacia (MESH:D010018), fragility fracture (MESH:D005600), erosions (MESH:D014077), mineralization (MESH:C537337), skeletal damage (MESH:C535850), chronic kidney disease (MESH:D051436), diabetes mellitus (MESH:D003920), synovitis (MESH:D013585), hepatitis B (MESH:D006509), seropositive (MESH:D006679), estrogen (MESH:D056828), BMD (MESH:D020388), autoimmune disease (MESH:D001327), Vitamin D insufficiency (MESH:D014808), joint destruction (MESH:D008105), thyroid disease (MESH:D013959), trauma (MESH:D014947), Osteoid (MESH:D010017), HIV infection (MESH:D015658), malabsorptive syndrome (MESH:D008286), deformity (MESH:D009140), stroke (MESH:D020521), neuromuscular disease (MESH:D009468), Bone Miner Metab (MESH:D012080), obesity (MESH:D009765), bone resorption (MESH:D001862), neoplasm (MESH:D009369), bone deterioration (MESH:D001847), death (MESH:D003643), cirrhosis (MESH:D005355), overweight (MESH:D050177), rheumatoid factor (MESH:D001171), rheumatic diseases (MESH:D012216)
- **Chemicals:** methyl methacrylate (MESH:D020366), tetracycline (MESH:D013752), vitamin D (MESH:D014807), S (MESH:D013455), 25-hydroxyvitamin D. (MESH:C104450), RA (MESH:D011883), BS (MESH:D001895), parathormone (MESH:D010281), prednisone (MESH:D011241), P (MESH:D010758), 25OHD (-), bisphosphonates (MESH:D004164), Ca (MESH:D002118), ethanol (MESH:D000431)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12981667/full.md

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Source: https://tomesphere.com/paper/PMC12981667