Effect of rhPTH(1-34) and alendronate on the treatment of type 2 diabetic bone disease

Huijuan Li^1,2,3Lingdan Yuan^1,2,3Peipei Liu⁴Yichen Liu^1,2Dongni Huang^1,2Huiru Ding^1,2Wei Jin^1,2,3Jingnan Liu^1,2,3Hong Xia Wang^1,2,3Lige Song^1,2,3*

• ¹Department of Endocrinology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China
• ²Department of Endocrinology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
• ³Institute of Osteoporosis and Metabolic Bone Diseases, School of Medicine, Tongji University, Shanghai, China
• ⁴Yichuan Community Health Service Center of Putuo District, Shanghai, China

Patients with type 2 diabetes mellitus (T2DM) have decreased bone turnover levels. However, there are few studies comparing the anti-osteoporosis effects of anabolic drugs and anti-resorptive drugs in patients with T2DM. Thus, this study was designed to compare the changes in bone mineral density (BMD) and bone turnover levels in mice and postmenopausal osteoporotic patients, both with and without T2DM, following treatment with rhPTH(1-34) or alendronate (ALN). The mouse model of T2DM (DM mice) was established by high-fat diet (60% from fat) feeding and streptozotocin injection (100 mg/kg) in C57BL/6 mice. Compared to control mice (CON mice), DM mice exhibited decreased bone mass, impaired bone microstructure and, decreased levels of bone turnover markers, including procollagen type I intact N-terminal (P1NP) and C terminal cross-linking telopeptide of type I collagen (CTX). rhPTH(1-34) could reverse the low bone turnover observed in DM mice and had a better effect on improving BMD, bone volume per tissue volume (BV/TV), trabecular number in femoral trabecular bone , as well as BMD, BV/TV, and trabecular thickness in lumbar trabecular bone. Then, a single-center, prospective, open-label, randomized controlled clinical study was conducted. Postmenopausal patients with osteoporosis (OP) and postmenopausal patients with both osteoporosis and type 2 diabetes (DOP) were recruited and randomly assigned to receive either rhPTH(1-34) or ALN treatment for a period of one year. At baseline, patients with DOP also exhibited decreased levels of bone turnover markers, including P1NP, CTX and osteocalcin. For patients with DOP, rhPTH(1-34) had a better effect than ALN on BMD improvement at the lumbar spine. Notably, the effect of ALN on lumbar spine improvement in patients with DOP was even smaller than that in patients with OP alone. These findings suggest that initiating treatment with rhPTH(1-34) may provide greater clinical benefits to patients with diabetic bone disease characterized by low bone turnover levels.