Enhanced bone remodeling in osteoporotic fracture healing by low-magnitude high-frequency vibration treatment

Enhanced bone remodeling in osteoporotic fracture healing by low-magnitude high-frequency vibration treatment

S410 Abstracts / Bone 47 (2010) S385–S458 femoral neck and total hip of adult sons from 400 nuclear families were 1.138 ± 0.137 g/cm2, 0.995 ± 0.141...

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Abstracts / Bone 47 (2010) S385–S458

femoral neck and total hip of adult sons from 400 nuclear families were 1.138 ± 0.137 g/cm2, 0.995 ± 0.141 g/cm2 and 1.008 ± 0.142 g/ cm2, respectively, whereas the same sites of BMD of unrelated elderly men group were 0.968 ± 0.153 g/cm2, 0.734 ± 0.112 g/cm2 and 0.833 ± 0.128 g/cm2, respectively. The genotype frequencies of six SNPs were in agreement with HapMap data. In the nuclear families, none of the tests for total association and within-family association by QTDT was significant between the six tagSNPs and BMD at the lumbar spine and hip sites. Likewise, no evidence of a positive correlation was found between three haplotype blocks and BMD at the same sites. Furthermore, no evidence of an association between the six tagSNPs and BMD in the elderly men group was found. Conclusion: These polymorphisms of the LRP2 gene might not be associated with the risk factors that contribute to BMD variation at specific sites in the Chinese male population. doi:10.1016/j.bone.2010.09.205

197 Infusion of ibandronate once every 3 months effectively decreases bone resorption markers and increases bone mineral density in Chinese postmenopausal osteoporotic women: A 1-year study Mei Li1, Xiao-ping Xing1, Zhen-lin Zhang2, Jian-li Liu3, Zhong-lan Zhang3, Dong-gang Liu4, Wei-bo Xia1, Xun-wu Meng1 1 Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China 2 Center for Preventing & Treating Osteoporosis, The 6th People's Hospital of Shanghai, Shanghai Jiaotong University, Shanghai, China 3 Department of Obstetrics & Gynecology, General Hospital of the People's Liberation Army, Beijing, China 4 Bio-Med Center, Hebei Medical University, Shijiazhuang, Hebei, China Objective: The efficacy and safety of intravenous ibandronate were evaluated in postmenopausal osteoporosis women in China. Method: In this multicenter, positive drug-controlled study, 158 postmenopausal osteoporotic women were randomized to receive 2 mg ibandronate given intravenously once every 3 months or 70 mg alendronate given orally once per week. All women also received supplemental calcium (500 mg) and vitamin D (200 IU) daily. One hundred fifty-one patients completed the 1-year study. Results: Ibandronate produced mean increases in bone mineral density (BMD) by 4.27% at the lumbar spine, 3.48% at the femoral neck and 2.03% at the trochanter. Mean increases in BMD by 4.24% at the lumbar spine, 2.72% at the femoral neck and 2.99% at the trochanter were observed in the alendronate group. No significant difference was found between the two groups in BMD in all sites measured. Significant decreases in serum c-telopeptide of type I collagen (CTX) and alkaline phosphatase (ALP) were found in the two groups after 1 and 3 months of treatment, respectively; these serum CTX and ALP levels were then maintained at the decreased levels throughout the study period (12 months). No changes of stature were found in the patients of the two groups. Adverse events were similar in the two groups, except more mild muscle pain was observed in the first month after infusion of ibandronate than with oral alendronate (p < 0.001). Conclusion: The results observed in Chinese patients may support the observation that intravenous ibandronate significantly reduced bone resorption and increased BMD with good tolerance in Chinese postmenopausal osteoporotic women. Use of intravenous ibandronate possibly could potentially improve compliance as compared with other oral bisphosphonates because it may avoid the peptic side effects of oral bisphosphonate. doi:10.1016/j.bone.2010.09.206

200 Efficacy of alendronate on children with osteogenesis imperfecta Mei Li, Wei-bo Xia, Xiao-ping Xing, Wei Yu, Yan Jiang, Ou Wang, Hai-juan Liu, Lan-wen Han, Ying-ying Hu, Xun-wu Meng Department of Endocrinology & Radiology, Peking Union Medical College Hospital, CAMS & PUMC, Beijing, China Objective: Osteogenesis imperfecta (OI) is a rare inherited bone disease characterized by multiple bone fractures. Previously, effective treatment was not available. This study tries to observe the effects of alendronate on bone mineral density, bone turnover markers and annual bone fracture rates in children with OI. Methods: One hundred and seven patients with OI were included receiving either alendronate (70 mg) weekly (n = 87) or calcitriol 0.25 μg daily (n = 20). At the same time, all patients took 500 mg calcium plus 250 IU Vitamin D daily. The observation period was 1 year. The bone mineral density (BMD), serum concentration of carboxy-telopeptide cross-links of type I collagen (CTX) and alkaline phosphatase (ALP) were measured, and annual fracture rate, growth speed, and activity ability were assessed. Results: Early onset of disease (85% earlier than 5 years old), multiple fractures (100%), extremity deformity (78%), short stature (92%), blue sclera (78%) and laxity of ligament (58%) were the main clinical manifestations of OI. One hundred and six cases completed the one year treatment. The concentration of CTX was significantly decreased by 42.6% rapidly after the three-month treatment of alendronate, BMD at the lumbar spine and total hip significantly increased by 59.0% and 36.6%, and the annual fracture rate decreased by 63.2% after the one year treatment of alendronate (as compared to pretreatment, p < 0.001). However, the level of CTX was significantly increased by 10.7% after the three-month treatment of calcitriol (as compared to pretreatment, p > 0.05), BMD at the lumbar spine and total hip significantly increased by 24.6% and 26.9%, as compared to pretreatment, p < 0.05, but the annual fracture rate was increased by 19%, as compared to pretreatment and alendronate, p < 0.001, after the one year treatment of calcitriol. Therefore, the benefit of alendronte to OI was more significant than that of calcitriol. No serious side effects and delayed fracture healing was found in these two treatment groups. Conclusion: This clinical study in a large sample of OI indicated that alendronate could significantly decrease bone resorption, increase BMD, reduce annual bone fracture rate and improve the life quality of children with OI.

doi:10.1016/j.bone.2010.09.207

201 Enhanced bone remodeling in osteoporotic fracture healing by low-magnitude high-frequency vibration treatment Wing-Hoi Cheung, Dick Ho-kiu Chow, Ling Qin, Kwok-sui Leung The Chinese University of Hong Kong, Hong Kong, China Objective: Low-magnitude high-frequency vibration (LMHFV) is a form of systemic, noninvasive, and cyclic mechanical stimulation. Our previous studies showed that LMHFV at 35 Hz and 0.3 g accelerated closed fracture healing by enhancing callus formation and mineralization in rats. Our hypothesis was that callus remodeling was enhanced by LMHFV treatment during fracture healing. To verify our hypothesis, ibandronate (Bis), a 2nd generation bisphosphonate, was used to block remodeling of callus by inducing osteoclast apoptosis and changes in remodeling were investigated. Methods: Closed femoral fracture was created on eighty female Sprague–Dawley rats that were 9 months old and ovariectomy-induced osteoporotics. The rats were randomly assigned into Control (CG), LMHFV (VG; 20 min/ day, 5 days/week), Bis (BG; 7 mg/kg/week), or LMHFV + Bis (VBG)

Abstracts / Bone 47 (2010) S385–S458

for a duration of 2, 4, 6, or 8 weeks. Both daily LMHFV and weekly injection of Bis were started 5 days post-operation until euthanasia. Callus area (CA) and width (CW), bone microarchitecture, mineral apposition rate (MAR), and serum biochemical markers (ostecalcin and TRAP5b) were measured with weekly radiography, end-point microCT, undecalcified histomorphometry and ELISA, respectively. Results: In weeks 4–8, radiographs and microCT showed VG had the fastest drop in CA, CW, and bone volume to tissue volume ratio (BV/ TV) and followed by CG; whereas, a plateaued trend in BG and VBG was observed. With respect to callus mineralization, VG showed the highest MAR at week 6. Similar MAR was found between VBG and CG; BG had the lowest MAR. Serum osteocalcin and TRAP5b in VG were higher than other groups at week 8. Discussion and conclusion: The fastest reduced CA and CW in VG indicated enhanced remodeling which was analogous to our previous study. The highest MAR suggested that LMHFV enhanced callus mineralization, an important process in callus remodeling. The increased serum markers implied increased osteoblastic and osteoclastic activities, which is associated with enhanced remodeling. Furthermore, LMHFV partially reversed the inhibition of bone remodeling by Bis suggested LMHFV had an opposite effect on bone remodeling to Bis. This is the first study to confirm that LMHFV accelerated osteoporotic fracture healing by enhancing bone remodeling. This study helps to understand the mechanism of fracture healing enhancement by LMHFV and the effects of LMHFV on bone remodeling. The enhanced remodeling by LMHFV may have great potential in clinical applications by allowing faster patient recovery. Acknowledgment This study has been supported by an OTC grant (ref. 131006-KSWH). doi:10.1016/j.bone.2010.09.208

202 Proteomics of osteoporosis in ovariectomized rats after low-magnitude and high-frequency mechanical vibration Renshi Ma1, Yuxian Yan2, Xu Huang1, Dong Zhu1, Xizheng Zhang3 1 First Hospital of Jilin University, Changchun, China 2 Department of Immunology of Medical College of CAPF, Tianjin, China 3 Institute of Medical Equipment, Military Medical Science Academy of the PLA, Tianjin, China Objective: Low magnitude and high-frequency mechanical vibration, with frequency of 32–37 Hz and acceleration of 0.2–0.3 g, can prevent osteoporosis and stimulate healing after bone fracture. The purpose of the research is to determine proteomics of osteoporosis in ovariectomized rats which are loaded by mechanical vibration and expression differences of marker protein related to treatment. Materials and methods: Twenty-one Sprague–Dawley rats were allocated into the following groups on average: CG (control group), CVG (continuous vibration group) and IVS (intermittent vibration group with interval of seven days). The osteoporosis model was established by suspension of the rats' tails, which is pasted by medical proof fabric linked to the metal stick at the top of animal's cage by a ring. Biomolecular testing was performed on the rats' right tibias after mechanical stimuli for eight weeks. The protein profile of pre- or post-vibration was addressed by two dimensional gel electrophoresis and LC-MS-MS/MS protein identification protocol. We identified 126 gene products, including proteins related to the extracellular matrix and ion transport, as well as enzymes, cytoskeletal and regulatory proteins. All the proteins were tested by Western blot. Results: By comparing with CG, 23 proteins in IVS are up regulated and 5 are down regulated, while 25 in CVG are increased and 2 are decreased. Conclusions: We identified the proteins which

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are differently expressed after mechanical vibration in osteoporotic rats. These proteins are considered as new candidate targets for osteoporosis which may be related to the mechanism or treatment for the disease and will be researched in the next step. Acknowledgments This work is supported by the National Natural Science Foundation of China (nos. 10832012 and 10872078) and the Scientific Advancing Front and Interdiscipline Innovation Project of Jilin University (no. 20090372). doi:10.1016/j.bone.2010.09.209

203 Low-magnitude, high-frequency mechanical signal appears to prevent osteoporosis in male suspended rats Dong Zhu1, Rui Zhang2, Dahui Sun1, Xizheng Zhang3, He Gong2 1 First Hospital of Jilin University, Changchun, China 2 College of Mechanism Science & Engineering, Jilin University, Changchun, China 3 Institute of Medical Equipment, Military Medical Science Academy of the PLA, Tianjin, China Objective: The purpose of the research is to determine whether the mechanical signal would prevent osteoporosis, especially the effect of vibration with short interval. Materials and methods: Forty-nine male Wistar rats, 3 months old, were allocated randomly into the following groups: SCG (suspension control group), CVG (continuous vibration group), IVO (intermittent vibration with interval of one day), IVT (intermittent vibration with interval of two days), IVF (intermittent vibration with interval of five days), IVS (intermittent vibration with interval of seven days) and CG (control group). All the rats were raised in the cages respectively, except the control group. The tails of the animals except the CG were pasted with medical proof fabric, which is linked to the metal stick at the top of the case by a ring. After suspension for one week, all the rats were loaded by low magnitude and high-frequency mechanical signal with different intervals, except that in SCG. The animals were loaded by mechanical stimuli, with a frequency of 32– 37 Hz and an acceleration of 0.3 g, for 15 min each day. The femurs were scanned by Micro-CT, and then were cut into slices for morphometry after sacrifice nine weeks later. Results: Morphometry: In all the vibration groups, the trabecular thickness is significantly higher than that in SCG. In sequence, the trabecular thickness showed an ascending order in the following groups: IVO, IVF, CVG, IVT and IVS. Micro-CT: the trabecular separation in all the vibration groups was significantly higher than that in SCG, which showed a dramatic osteoporosis. IVS can obviously prevent the osteoporosis, as well as the beneficial effect shown in IVF and CVG. Conclusions: The disuse osteoporosis model is perfectly established by this less invasive procedure. Intermittent vibration with different intervals can prevent the osteoporosis. The best effect is obtained in the vibration group with an interval of seven days. However, its clinical application and long-term outcome is still under inspection. Acknowledgments This work is supported by the National Natural Science Foundation of China (nos. 10832012 and 10872078) and the Scientific Advancing Front and Interdiscipline Innovation Project of Jilin University (no. 20090372).

doi:10.1016/j.bone.2010.09.210