Research Article: Different bone sites-specific response to diabetes rat models: Bone density, histology and microarchitecture

Date Published: October 22, 2018

Publisher: Public Library of Science

Author(s): Yunwei Hua, Ruiye Bi, Yue Zhang, Luchen Xu, Jiaoyang Guo, Yunfeng Li, Deepak Vashishth.

http://doi.org/10.1371/journal.pone.0205503

Abstract

Diabetes mellitus (DM) is the most common metabolic disorder that is characterized by hyperglycemia, it can be categorized by T1DM and T2DM. T1DM is also reported to cause bone loss. However, most reports regarding this aspect of T1DM have only investigated a single site; a comparison of bone loss from different areas of the body is still lacking.

Thirty-five 12-week-old Sprague Dawley® (SD) rats were separated to seven groups. Five rats were euthanized without any surgery at 0 weeks for histological examination and determination of baseline characteristics. In 15 of the rats, DM was induced via Streptozotocin (STZ)-injection, and they were separated to 3 groups (4 weeks, 8 weeks and 12 weeks after STZ-injection). The remaining 15 rats were used as the control group (4 weeks, 8 weeks and 12 weeks after saline-injection). We tested bone-mass loss at four skeletal sites, the tibia, the femur greater trochanter, the spine, and the mandibular bones using micro-computed tomography (CT) and histological tests.

Tibia was influenced the most obvious(BV/TV decreased by 27.3%, 52.5%, and 81.2% at 4 weeks, 8 weeks, and 12 weeks, respectively. p<0.05). In contrast, the other three sites were influenced to a lesser extent and bone loss became prominent at a later time point according to the histological and micro-CT tests(Femur: BV/TV did not decrease significantly at the first month or second month. However, and decreased by 49.4% at the third month, P<0.05. Mandible: the BV/TV only decreased by 6.5% at 1 month after STZ-injection. There was still a significant difference between the second and third months. The BV/TV decreased by 47.0% and 68.1% at 2 months and 3 months, respectively, (p<0.05) Spine: the BV/TV only decreased by 6.7%. However, significant change was observed in the spine at the second month and third month after STZ injection. The BV/TV decreased by 45.4% and 64.3%, respectively, p<0.05). The results indicate that T1DM can severely influence the bone structure of the 4 skeletal sites. Further, areas with dense trabecular bones were influenced less and at a later time point in comparison to the tibial region. Our research can serve as a guide to help increase the success rate of implant treatment, and help decrease the fracture risk in different bone types with greater accuracy.

Partial Text

Diabetes mellitus (DM) is the most common metabolic disorder characterized by hyperglycemia and associated with many diseases, such as retinopathy, nephropathy, cardiovascular disease, and osteoporosis [1]. In 2012, the prevalence of diabetes in adults between the ages of 20 and 79 years worldwide was estimated at about 382 million persons, and it was likely to increase to 592 million people by 2035.[2] In the United States of America (USA), the prevalence of DM has reached 10.9%. Approximately $101.4 billion (uncertainty interval [UI], $96.7–106.5 billion) was spent on diabetes in the USA, including 57.6% spent on pharmaceuticals and 23.5% (UI, 21.7–25.7%) spent on ambulatory care, which was the highest health care expense in 2013 [3]. China also has a large health burden of diabetes: in 2013, a quarter of diabetic patients worldwide were in China, where 11.6% of adults had diabetes and 50.1% had prediabetes.[4] DM can be divided into type I diabetes (insulin-dependent) and type II diabetes (non-insulin-dependent). Both of these 2 kinds of DM can cause hyperglycemia and several chronic bone metabolic diseases, including diabetic osteoporosis (DOP).[5]

Recent studies have reported that diabetes can affect bone quality and lead to bone loss, causing fracture and osteoporosis[21]. In addition, bone loss can also impair implant osseointegration in orthopedic and dental treatments [22]. Implant treatments can be used at many sites, such as the mandibular bones, tibia, and hip. Thus we aimed to investigate whether diabetic osteoporosis also leads to a different severity of bone loss at different bone sites. In our study, we separately clarified different phenomena of diabetic osteoporosis at different bone sites, including the proximal tibia, femur, mandibular bone, and spine, in rats with T1DM and we found that the areas with dense trabecular bones were influenced less and at a later time point in comparison to the tibial region. Moreover, our research can be used to help physicians clinically prevent fractures due to diabetic osteoporosis. It can also provide physicians with more implant treatment options for diabetic patients.

We conclude that DOP affects the quality of all 4 skeletal sites, especially in long bones, and DOP also has milder and postponed effect on the mandibular bones, spine, and greater trochanter. In locations with dense cancellous bone, the effect is less than that in the areas without dense cancellous bone, and it is always accompanied with hysteresis. This information can help physicians prevent patients with DOP from developing fractures and provide more sensitively treatment options, including implants. Patients with DOP may easily develop fractures of the long bones and other sites that lack cancellous bone, and the risk of implant failure may increase at these sites. Although these patients have a diabetic disease, the success rate of implants might be comparatively higher in areas of dense trabecular bone.

 

Source:

http://doi.org/10.1371/journal.pone.0205503

 

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