薬理と治療

Abstract

Objectives Type 2 diabetic patients have increased fracture risk and lower bone mineral density（BMD）. However, there are few reports concerning BMD and type 2 diabetes. In this study we examined whether or not BMD is lower in Japanese type 2 diabetic patients. Receptor activator of nuclear factor NF-kappaB ligand （RANCL）produced by osteoblastic cells is the essential factor for osteoclast formation, activation and survival, thus resulting in bone resorption and bone loss. From this point of view denosumab was developed as anti-RANCL antibody for the treatment of osteoporosis. Little information is available about the effects of denosumab on diabetic osteopenia. We examined the effects of denosumab or bisphosphonate in diabetic patients after 2 years treatment of teriparatide. Methods We evaluated lumbar spine BMD and femoral（proximal part）BMD in 21 diabetic patients and 11 non-diabetic subjects（50-59 years of age, female）, 35 diabetic patients and 72 non-diabetic subjects（60-69 years of age, female）, 44 diabetic patients and 272 non-diabetic subjects（70-79 years of age, female）, and 27 diabetic patients and 267 non︱diabetic subjects （80-89 years of age, female）. BMD was evaluated with dual energy X-ray absorptiometry （DEXA）according to the guideline of Japan Osteoporosis Society 2015. BMD was expressed as the percent ratio to the young adult mean BMD（20︱29 years of age）. The effects of denosumab or bisphosphonate on diabetic osteopenia after 2 years treatment of teriparatide were examined. Fifteen diabetic patients took bisphosphonate （alendronate 35 mg weekly or risedronate 17.5 mg weekly）for 1.5 years after 2 years treatment of teriparatide（20μg daily）, whereas 32 diabetic patients took denosumab（60 mg every 6 months）for 1.5 years after 2 years treatment of teriparatide（20μg daily）. BMD was checked before and 2 years after the treatment of teriparatide, and then 1 year and 1.5 years after the treatment of denosumab or bisphosphonate. Results In any age group diabetic patients had significantly（P＜0.01）lower lumbar spine BMD and femoral BMD than non-diabetic controls. In 15 diabetic patients who took bisphosphonate after 2 years teriparatide treatment lumbar spine BMD was 78.7％ after 2 years teriparatide treatment, and then 80.3％ after 1 year bisphosphonate treatment and 77.1％ after 1.5 years bisphosphonate treatment, whereas femoral BMD was 73.9％ after 2 years teriparatide treatment, and then 75.3％ after 1 year bisphosphonate treatment and 70.7％ after 1.5 years bisphosphonate treatment. There was no significant difference in BMD between 2 years teriparatide treatment and 1 year or 1.5 years bisphosphonate treatment. In 32 diabetic patients who took denosumab after 2 years teriparatide treatment lumbar spine BMD was 77.4％ after 2 years teriparatide treatment, and then 87.9％ after 1 year denosumab treatment and 94.3％ after 1.5 years denosumab treatment, whereas femoral BMD was 73.8％ after 2 years teriparatide treatment, and then 80.9％ after 1 year denosumab treatment and 88.8％ after 1.5 years denosumab treatment. BMD significantly（P＜0.01）increased after 1 year and 1.5 years denosumab treatment compared to BMD after 2 years teriparatide treatment. Conclusions This study clearly showed that type 2 diabetic patients had lower BMD than the age-matched non-diabetic subjects, suggesting the existence of osteopenia in diabetes mellitus. For diabetic osteopenia denosumab therapy after teriparatide treatment is more effective than bisphosphonate.