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Okubo A1
1Teikyo Heisei University, Department of Physical Therapy, Tokyo, Japan
Background: The major pathophysiology of osteoporosis is bone vulnerability and fracture, which causes disability to the activity of the elderly. A mechanical stimulation, such as gravity, is indispensable for bone formation. Providing appropriate mechanical stress as treatments is the most important part that therapists contribute. Although the main drug in osteoporosis medication therapy was an osteoclast inhibitor, there was a problem that osteogenesis also could be inhibited in a chain reaction manner. Recombinant human parathyroid hormone (PTH) has been approved recently as the first osteoporosis treatment that leads to the formation of new bone with architecture similar to normal bone. However, it has not been revealed what effect will be produced when mechanical stimulation is applied to the bone of a patient undergoing PTH treatment.
Purpose: Senescence-accelerated mouse prone 6 (SAMP6) was used as a model of low-turnover osteoporosis. The objective was to examine the effect of the combined use of mechanical vibration by LIPUS (Low-Intensity Pulsed Ultrasound) that promotes the differentiation of osteoblasts and PTH therapeutic administration. States of osteogenesis were assessed compared to senescence-accelerated mouse resistant 1 (SAMR1) as a control model.
Methods: SAMP6 and SAMR1 of 17 to 20-week-old mice were used. PTH subcutaneous administration (20 µg / kg BW) and LIPUS irradiation (30 mW / cm2, 20 min.) to the right femur were performed five times a week. After 1 and 3 weeks, serum and both femurs were collected. The amounts of Gla-Osteocalcin (Gla-OC) in serum were analyzed by EIA, and the bone structure analysis of the distal femur in the frontal plane by µCT was performed. For each data, the one-way analysis of variance and multiple comparison were performed. The level of significance was set at 5%.
Results: The serum concentration of Gla-OC reflecting the osteoblast activity was lower in the SAMP6 group than in the SAMR1 group. At 1 week, the level of Gla-OC significantly increased by using a combination of PTH and US in both the SAMR1 group and the SAMP6 group. Although the Gla-OC level of the SAMP 6 group itself was low, the combination treatment was slightly more effective than the SAMR 1 group. In the bone structure analysis of cancellous bone, though there was no difference in the number of trabecular bone, the trabecular bone width was the most increased on the combined treatment side of the SAMR1 group and showed a significant difference from the non-combined treatment bone and non-treatment bone of the SAMP6 group. At 3 weeks, the cancellous bone ratio was the lowest in the non-treatment bone of the SAMP6 group (7.91 ± 1.45%) and highest in combined treatment bone of the SAMP1 (12.54 ± 3.06%).
Conclusion(s): The osteoblasts in low-turnover osteoporosis were less differentiated than normal osteoblasts and responsiveness to mechanical stimuli could also be reduced. However, the combined use of PTH and LIPUS could improve the bone mass and bone structure of elderly patients with osteoporosis.
Implications: This study showed that applying the appropriate mechanical stress to elderly low-turnover osteoporotic patients undergoing PTH administration was effective in improving bone strength.
Keywords: Osteoporosis, low-intensity pulsed ultrasound, parathyroid hormone
Funding acknowledgements: This work was supported by JSPS KAKENHI Grant Number JP25750220.
Purpose: Senescence-accelerated mouse prone 6 (SAMP6) was used as a model of low-turnover osteoporosis. The objective was to examine the effect of the combined use of mechanical vibration by LIPUS (Low-Intensity Pulsed Ultrasound) that promotes the differentiation of osteoblasts and PTH therapeutic administration. States of osteogenesis were assessed compared to senescence-accelerated mouse resistant 1 (SAMR1) as a control model.
Methods: SAMP6 and SAMR1 of 17 to 20-week-old mice were used. PTH subcutaneous administration (20 µg / kg BW) and LIPUS irradiation (30 mW / cm2, 20 min.) to the right femur were performed five times a week. After 1 and 3 weeks, serum and both femurs were collected. The amounts of Gla-Osteocalcin (Gla-OC) in serum were analyzed by EIA, and the bone structure analysis of the distal femur in the frontal plane by µCT was performed. For each data, the one-way analysis of variance and multiple comparison were performed. The level of significance was set at 5%.
Results: The serum concentration of Gla-OC reflecting the osteoblast activity was lower in the SAMP6 group than in the SAMR1 group. At 1 week, the level of Gla-OC significantly increased by using a combination of PTH and US in both the SAMR1 group and the SAMP6 group. Although the Gla-OC level of the SAMP 6 group itself was low, the combination treatment was slightly more effective than the SAMR 1 group. In the bone structure analysis of cancellous bone, though there was no difference in the number of trabecular bone, the trabecular bone width was the most increased on the combined treatment side of the SAMR1 group and showed a significant difference from the non-combined treatment bone and non-treatment bone of the SAMP6 group. At 3 weeks, the cancellous bone ratio was the lowest in the non-treatment bone of the SAMP6 group (7.91 ± 1.45%) and highest in combined treatment bone of the SAMP1 (12.54 ± 3.06%).
Conclusion(s): The osteoblasts in low-turnover osteoporosis were less differentiated than normal osteoblasts and responsiveness to mechanical stimuli could also be reduced. However, the combined use of PTH and LIPUS could improve the bone mass and bone structure of elderly patients with osteoporosis.
Implications: This study showed that applying the appropriate mechanical stress to elderly low-turnover osteoporotic patients undergoing PTH administration was effective in improving bone strength.
Keywords: Osteoporosis, low-intensity pulsed ultrasound, parathyroid hormone
Funding acknowledgements: This work was supported by JSPS KAKENHI Grant Number JP25750220.
Topic: Musculoskeletal: lower limb; Older people; Musculoskeletal: lower limb
Ethics approval required: Yes
Institution: Teikyo Heisei University
Ethics committee: the Ethical Committee of Teikyo Heisei University
Ethics number: 29-001
All authors, affiliations and abstracts have been published as submitted.
