Effect of genetic polymorphisms of aldehyde dehydrogenase 2 on the efficacy of intermittent parathyroid hormone treatment and bone mineral density: A retrospective multicenter study
10.1016/j.afos.2026.02.002
- Author:
Hinako OBARA
1
;
Takafumi TAJIMA
;
Manabu TSUKAMOTO
;
Yoshiaki YAMANAKA
;
Hitoshi SUZUKI
;
Masato NAGASHIMA
;
Satoshi NISHIDA
;
Satoshi IKEDA
;
Kazumichi MAEKAWA
;
Akinori SAKAI
Author Information
1. Department of Orthopaedic Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan
- Publication Type:Original article
- From:Osteoporosis and Sarcopenia
2026;12(1):26-33
- CountryRepublic of Korea
- Language:English
-
Abstract:
Objectives:In a mouse model, aldehyde dehydrogenase 2 (ALDH2) knockout resulted in lower bone mineral density; however, higher parathyroid hormone receptor expression than wild-type mice. This study aimed to investigate whether ALDH2 polymorphisms influence efficacy of intermittent parathyroid hormone therapy and bone mineral density changes in humans.
Methods:Eighty-two patients with primary osteoporosis treated with parathyroid hormone for > 1 year were divided into wild-type ALDH2 (ALDH2*1) and variant (ALDH2*2) groups. Bone mineral densities were measured by dual-energy X-ray absorptiometry. Changes in bone mineral density, treatment response, bone turnover markers, and new fracture incidence were evaluated. Furthermore, bone mineral density was analyzed using a mixed-effects model.
Results:Femoral neck bone mineral density increased by 1.0 ± 7.4% in the ALDH2*1 group and 4.3 ± 8.1% in the ALDH2*2 group (P < 0.05), whereas lumbar spine bone mineral density increased by 5.7 ± 8.2% and 9.4 ± 9.1% without significance. Treatment success rates were higher in ALDH2*2 group (femoral neck 38.7%, lumbar spine 68.8%) compared with ALDH2*1 (16.3%, 51.0%). Statistical significance was observed only at the femoral neck. Bone turnover markers and fracture incidence were comparable between groups. Mixed-effects analysis adjusting for confounders showed a significant ALDH2 genotype × duration interaction for femoral neck, indicating genotype-related differences in the rate of bone mineral density increase over time. For lumbar spine, the genotype main effect was significant, whereas the interaction was not.
Conclusions:These findings suggest that ALDH2 polymorphisms may influence the therapeutic response to PTH treatment and highlight the need for larger future studies.
