Effects of teriparatide on bone in autochthonous transgenic model mice for diabetes mellitus (Akita mice)

OBJECTIVES@#The purpose of this study is to evaluate the effects of teriparatide (TPTD) on bone mineral density (BMD), bone strength, and bone quality in Akita mouse models of diabetes mellitus.@*METHODS@#Twelve-week-old female Akita mice and control mice (C57/BL/6NCrSlc) were divided into 4 groups: control mice treated with vehicle (n = 7) or TPTD (n = 6); and Akita mice treated with vehicle (n = 6) or TPTD (n = 7). TPTD or vehicle was administered subcutaneously 3 times a week for 8 weeks. Blood glucose, serum sclerostin, total tibial BMD, femoral shaft bone strength, and bone quality using Fourier-transform infrared spectroscopy imaging were evaluated.@*RESULTS@#No significant differences in serum sclerostin levels were evident among these groups after 8 weeks of treatment. TPTD significantly increased BMD in control mice (+12.7%, P = 0.02) and Akita mice (+29.2%, P = 0.001) compared with vehicle. Maximum load and stiffness were significantly higher in Akita mice treated with TPTD than in Akita mice treated with vehicle (+56.6%, P = 0.03 and + 90.5%, P = 0.02, respectively). On Fourier-transform infrared spectroscopy imaging, the mineral/matrix ratio was significantly lower in Akita mice treated with vehicle than in control mice (−12.2%, P = 0.02), and TPTD treatment significantly increased the mineral/matrix ratio (P = 0.003).@*CONCLUSIONS@#TPTD thus improved BMD and bone strength in both control mice and Akita mice, with improvements in the mineral/matrix ratio among Akita mice.

Combined treatment with minodronate and vitamin C increases bone mineral density and strength in vitamin C-deficient rats

OBJECTIVES: Reduced bone quality caused by vitamin C deficiency in older persons may lead to incidental fragility fractures during bisphosphonate treatment, although bisphosphonate increases bone mineral density (BMD). This study aimed to evaluate the effects of minodronate and ascorbic acid (Aa) on BMD, bone quality, and bone strength in Aa(-)deficient osteogenic disorder Shionogi (ODS) rats. METHODS: Six-month-old ODS rats were divided into four groups (n = 20 per group): (1) Aa supplementation (Aa(+)); (2) Aa(-)deficient (Aa(-)); (3) Aa supplementation and minodronate administration (Aa(+) + Mino); and (4) Aa(-)deficient and minodronate administration (Aa(-) + Mino). BMD, bone strength, bone histomorphometry, and bone quality determined using Fourier transform infrared spectroscopy imaging (FTIRI) were evaluated after 4 and 8 weeks. RESULTS: BMD was significantly higher in the Aa(+) + Mino group than in the Aa(-) group (p < 0.05). Bone strength was significantly higher in the Aa(+) and Aa(+) + Mino groups than in the Aa(-) group (p < 0.05). Furthermore, bone strength was significantly higher in the Aa(+) + Mino group than in the Aa(-) + Mino group (p < 0.05). Minodronate treatment irrespective of Aa supplementation significantly decreased bone resorption compared with the Aa(+) and Aa(-) groups (p < 0.05). No significant differences in the parameters evaluated by FTIRI were observed between the groups. CONCLUSIONS: Aa supplementation improved bone strength in ODS rats. Combined treatment with minodronate and Aa, but not minodronate alone, improved bone strength and increased BMD. Aa is required for bone health because it is essential for osteoblast differentiation.

Occurrence of vertebral fracture more closely associated with decreased anteroposterior than lateral lumbar bone mineral density

OBJECTIVES: While it has been pointed out that an anteroposterior (AP) view of the lumbar spine may lead to overestimation of the bone mineral density (BMD), a lateral view is expected lead to the early detection of BMD loss on scanning cancellous bone. Vertebral fracture is often seen in aged osteoporotic patients, and it is important to prevent this fracture. Therefore, we aimed to identify the optimal site for BMD measurement to assess the risk of vertebral fracture. METHODS: Forty-seven female patients with fresh osteoporotic vertebral fracture and BMD measurements were included in this study (Fracture group). As a non-fractured control group, 218 female patients with BMD measurements were enrolled (Control group). We compared BMD values based on AP and lateral views of the lumbar spine from L2 to L4 and the femoral neck. With a lateral view of the lumbar spine, we measured both the total vertebral body and vertebral body center, mainly composed of cancellous bone. RESULTS: BMD of the AP lumbar spine in the Fracture group was significantly lower than in the Control group (P < 0.05). In the subanalyses for comparisons between age-matched fracture and control groups, BMD of only the AP lumbar spine in the Fracture group was significantly lower than in the Control group (P < 0.01). CONCLUSIONS: AP lumbar spine BMD is optimal for assessing vertebral fracture occurrence.