Clinical and bone-turnover outcomes associated with topical herbal plaster adjunctive therapy in older patients with myasthenia gravis and glucocorticoid-associated osteoporotic fragility fracture: a retrospective cohort study with exploratory peripheral-blood BMP-2/Smad/Runx2 analysis
- 1Department of Geriatric Orthopaedics, Sichuan Province Orthopedic Hospital
- 2Department of Anesthesiology, Affiliated Sport Hospital of CDSU
Abstract
Background: Elderly patients with myasthenia gravis (MG) frequently require prolonged glucocorticoid therapy and may develop glucocorticoid-associated osteoporosis and fragility fracture. Post-fracture recovery in this population may be complicated by neuromuscular weakness, fall risk, impaired bone remodeling, fracture-site pain, and limited tolerance of systemic analgesic therapy. Xiaotong plaster is a topical external therapy used for musculoskeletal pain and swelling, but evidence for its adjunctive use after osteoporotic fracture in elderly patients with MG remains limited.
Objective: This study evaluated the association between Xiaotong plaster adjunctive external treatment and 12-week fracture-site pain in elderly MG patients with glucocorticoid-associated osteoporotic fragility fracture. Bone-turnover and inflammatory outcomes were assessed as secondary exploratory endpoints, and BMP-2/Smad/Runx2-related changes were evaluated as hypothesis-generating mechanistic signals. These peripheral-blood measurements were treated as exploratory correlates and not as evidence that the topical plaster activated an osteogenic pathway at the fracture site.
Methods: Consecutive patients aged 60 years or older with confirmed MG, systemic glucocorticoid exposure for at least 3 months, and radiologically confirmed osteoporotic fragility fracture were retrospectively screened at a tertiary medical center between January 2021 and December 2025. Patients receiving standard anti-osteoporosis treatment alone were compared with those receiving standard treatment plus Xiaotong plaster within 4 weeks after fracture. The primary outcome was fracture-site pain change from baseline to 12 weeks. Secondary and biomarker outcomes were considered exploratory. Propensity score weighting was used to reduce measured baseline imbalance, with doubly robust and sensitivity analyses used to examine the robustness of the primary association. Treatment allocation was observational and unblinded; no placebo plaster was used.
Results: A total of 168 patients were included, including 86 receiving standard treatment alone and 82 receiving standard treatment plus Xiaotong plaster. The adjusted between-group difference in 12-week pain change was −10.2 mm on the 0–100 mm scale (95% CI, −13.8 to −6.6; P < 0.001). P1NP increased more in the adjunctive-treatment group (adjusted difference, 10.2 ng/mL; 95% CI, 6.8 to 13.6; P < 0.001), while β-CTX decreased modestly more (adjusted difference, −0.045 ng/mL; 95% CI, −0.087 to −0.003; P = 0.035). Six-month radiographic healing (P = 0.711), delayed union or nonunion (P = 0.363), 12-month new fragility fracture (P = 0.083), lumbar spine BMD change (P = 0.177), and MG exacerbation (P = 0.692) did not differ significantly after adjustment. In the exploratory subgroup, p-Smad1/5/8 (P = 0.001) and Runx2 (P = 0.002) increased more in the adjunctive-treatment group, whereas BMP-2 change was not significant (P = 0.449). The biomarker signal was therefore confined to downstream p-Smad1/5/8 and Runx2 rather than BMP-2 itself. One exposed patient permanently discontinued the plaster because of contact dermatitis.
Conclusion: Xiaotong plaster adjunctive treatment was associated with greater short-term fracture-site pain reduction and exploratory changes in bone-turnover markers in elderly MG patients with glucocorticoid-associated osteoporotic fragility fracture. The study did not demonstrate improvement in fracture healing, BMD, or recurrent fracture, and the peripheral-blood BMP-2/Smad/Runx2 findings should be interpreted as hypothesis-generating rather than evidence of a causal osteogenic mechanism. Human transdermal pharmacokinetic exposure was not measured, so systemic pathway activation cannot be inferred from these data.
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BibTeX
@article{pan2026clinical,
title = {{Clinical and bone-turnover outcomes associated with topical herbal plaster adjunctive therapy in older patients with myasthenia gravis and glucocorticoid-associated osteoporotic fragility fracture: a retrospective cohort study with exploratory peripheral-blood BMP-2/Smad/Runx2 analysis}},
author = {Qing Pan and Wei Wei and Chengjie Tang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1929809},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1929809/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clinical and bone-turnover outcomes associated with topical herbal plaster adjunctive therapy in older patients with myasthenia gravis and glucocorticoid-associated osteoporotic fragility fracture: a retrospective cohort study with exploratory peripheral-blood BMP-2/Smad/Runx2 analysis
AU - Qing Pan
AU - Wei Wei
AU - Chengjie Tang
PY - 2026
DA - 2026/10/19
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1929809
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1929809/full
AB - Background: Elderly patients with myasthenia gravis (MG) frequently require prolonged glucocorticoid therapy and may develop glucocorticoid-associated osteoporosis and fragility fracture. Post-fracture recovery in this population may be complicated by neuromuscular weakness, fall risk, impaired bone remodeling, fracture-site pain, and limited tolerance of systemic analgesic therapy. Xiaotong plaster is a topical external therapy used for musculoskeletal pain and swelling, but evidence for its adjunctive use after osteoporotic fracture in elderly patients with MG remains limited. Objective: This study evaluated the association between Xiaotong plaster adjunctive external treatment and 12-week fracture-site pain in elderly MG patients with glucocorticoid-associated osteoporotic fragility fracture. Bone-turnover and inflammatory outcomes were assessed as secondary exploratory endpoints, and BMP-2/Smad/Runx2-related changes were evaluated as hypothesis-generating mechanistic signals. These peripheral-blood measurements were treated as exploratory correlates and not as evidence that the topical plaster activated an osteogenic pathway at the fracture site. Methods: Consecutive patients aged 60 years or older with confirmed MG, systemic glucocorticoid exposure for at least 3 months, and radiologically confirmed osteoporotic fragility fracture were retrospectively screened at a tertiary medical center between January 2021 and December 2025. Patients receiving standard anti-osteoporosis treatment alone were compared with those receiving standard treatment plus Xiaotong plaster within 4 weeks after fracture. The primary outcome was fracture-site pain change from baseline to 12 weeks. Secondary and biomarker outcomes were considered exploratory. Propensity score weighting was used to reduce measured baseline imbalance, with doubly robust and sensitivity analyses used to examine the robustness of the primary association. Treatment allocation was observational and unblinded; no placebo plaster was used. Results: A total of 168 patients were included, including 86 receiving standard treatment alone and 82 receiving standard treatment plus Xiaotong plaster. The adjusted between-group difference in 12-week pain change was −10.2 mm on the 0–100 mm scale (95% CI, −13.8 to −6.6; P < 0.001). P1NP increased more in the adjunctive-treatment group (adjusted difference, 10.2 ng/mL; 95% CI, 6.8 to 13.6; P < 0.001), while β-CTX decreased modestly more (adjusted difference, −0.045 ng/mL; 95% CI, −0.087 to −0.003; P = 0.035). Six-month radiographic healing (P = 0.711), delayed union or nonunion (P = 0.363), 12-month new fragility fracture (P = 0.083), lumbar spine BMD change (P = 0.177), and MG exacerbation (P = 0.692) did not differ significantly after adjustment. In the exploratory subgroup, p-Smad1/5/8 (P = 0.001) and Runx2 (P = 0.002) increased more in the adjunctive-treatment group, whereas BMP-2 change was not significant (P = 0.449). The biomarker signal was therefore confined to downstream p-Smad1/5/8 and Runx2 rather than BMP-2 itself. One exposed patient permanently discontinued the plaster because of contact dermatitis. Conclusion: Xiaotong plaster adjunctive treatment was associated with greater short-term fracture-site pain reduction and exploratory changes in bone-turnover markers in elderly MG patients with glucocorticoid-associated osteoporotic fragility fracture. The study did not demonstrate improvement in fracture healing, BMD, or recurrent fracture, and the peripheral-blood BMP-2/Smad/Runx2 findings should be interpreted as hypothesis-generating rather than evidence of a causal osteogenic mechanism. Human transdermal pharmacokinetic exposure was not measured, so systemic pathway activation cannot be inferred from these data.
SN - 1664-3224
ER -