Effect of alendronate on muscle mass: Investigation in patients with osteoporosis

Harada, Atsushi; Ito, Sadayuki; Matsui, Yasumoto; Sakai, Yoshihito; Takemura, Marie; Tokuda, Harukuni; Hida, Takeyuki; Shimokata, Hiroshi

doi:10.1016/j.afos.2015.07.005

Cited by 21 publications

(22 citation statements)

References 27 publications

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“…We used a well‐established murine model of skeletal muscle atrophy‐denervation‐induced muscle atrophy instead of using an osteoporotic murine model to investigate the effect of ALN on muscle wasting. We hypothesized that this anti‐osteoporosis drug could effectively not only enhance skeletal muscle mass and strength in patients with osteoporosis but also improve skeletal muscle loss and dysfunction from cachexia, sarcopenia, and other muscle wasting‐related diseases. These findings suggest that ALN can be a promising therapeutic strategy for management of muscle wasting‐related diseases and sarcopenia.…”

Section: Discussionmentioning

confidence: 99%

“…Alendronate (ALN), the most popular first‐line bisphosphonate drug, has been widely used for the treatment of osteoporosis by increasing bone density and micro‐architecture and prohibiting bone resorption in the elderly and postmenopausal women . Due to the hazardous duet of the decline in bone mineral density (osteoporosis) and muscle mass (sarcopenia) leading to frailty, recent reports on the treatment of the osteoporosis with ALN or other bisphosphonates have also indicated that these anti‐osteoporosis drugs provided a positive effect on muscle mass and strength in osteoporotic patients . However, Widrick et al .…”

Section: Introductionmentioning

confidence: 99%

“…11,12 Due to the hazardous duet of the decline in bone mineral density (osteoporosis) and muscle mass (sarcopenia) leading to frailty, recent reports on the treatment of the osteoporosis with ALN or other bisphosphonates have also indicated that these anti-osteoporosis drugs provided a positive effect on muscle mass and strength in osteoporotic patients. [13][14][15] However, Widrick et al have found that ALN can improve bone loss but has no independent effect on muscle function in ovariectomized rats, an animal model of post-menopausal osteoporosis. 16 Therefore, the effect and mechanism of ALN on skeletal muscle function still remain to be clarified and in need of further investigation.…”

Section: Introductionmentioning

confidence: 99%

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Preventing muscle wasting by osteoporosis drug alendronate in vitro and in myopathy models via sirtuin‐3 down‐regulation

Chiu

Yang

et al. 2018

J cachexia sarcopenia muscle

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Background A global consensus on the loss of skeletal muscle mass and function in humans refers as sarcopenia and cachexia including diabetes, obesity, renal failure, and osteoporosis. Despite a current improvement of sarcopenia or cachexia with exercise training and supportive therapies, alternative and specific managements are needed to discover for whom are unable or unwilling to embark on these treatments. Alendronate is a widely used drug for osteoporosis in the elderly and postmenopausal women. Osteopenic menopausal women with 6 months of alendronate therapy have been observed to improve not only lumbar bone mineral density but also handgrip strength. However, the effect and mechanism of alendronate on muscle strength still remain unclear. Here, we investigated the therapeutic potential and the molecular mechanism of alendronate on the loss of muscle mass and strength in vitro and in vivo. Methods Mouse myoblasts and primary human skeletal muscle-derived progenitor cells were used to assess the effects of low-dose alendronate (0.1-1 μM) combined with or without dexamethasone on myotube hypertrophy and myogenic differentiation. Moreover, we also evaluated the effects of low-dose alendronate (0.5 and 1 mg/kg) by oral administration on the limb muscle function and morphology of mice with denervation-induced muscle atrophy and glycerol-induced muscle injury. Results Alendronate inhibited dexamethasone-induced myotube atrophy and myogenic differentiation inhibition in mouse myoblasts and primary human skeletal muscle-derived progenitor cells. Alendronate significantly abrogated dexamethasone-up-regulated sirtuin-3 (SIRT3), but not SIRT1, protein expression in myotubes. Both SIRT3 inhibitor AKG7 and SIRT3-siRNA transfection could also reverse dexamethasone-up-regulated atrogin-1 and SIRT3 protein expressions. Animal studies showed that low-dose alendronate by oral administration ameliorated the muscular malfunction in mouse models of denervation-induced muscle atrophy and glycerol-induced muscle injury with a negative regulation of SIRT3 expression. Conclusions The putative mechanism by which muscle atrophy was improved with alendronate might be through the SIRT3 down-regulation. These findings suggest that alendronate can be a promising therapeutic strategy for management of muscle wasting-related diseases and sarcopenia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preventing muscle wasting by osteoporosis drug alendronate in vitro and in myopathy models via sirtuin‐3 down‐regulation

Chiu

Yang

et al. 2018

J cachexia sarcopenia muscle

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“…In addition, a recent clinical study indicated that alendronate increases the muscle mass of osteoporosis patients [17]. We should note that the direct impact of alendronate on myogenic cells highly depends on its dosage.…”

Section: Discussionmentioning

confidence: 98%

Impairment of cold injury-induced muscle regeneration in mice receiving a combination of bone fracture and alendronate treatment

2017

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Alendronate, a nitrogen-containing bisphosphonate, is well established as a treatment for osteoporosis through regulation of osteoclast activity. Previously, the pharmacological effects of bisphosphonates on cells outside the bone environment have been considered irrelevant because bisphosphonates target bone. Here we show that administration of alendronate impairs muscle regeneration in mice after bone fracture. A series of injections of alendronate alone or bone fracture alone did not affect muscle regeneration induced by cold injury. In contrast, alendronate treatment plus bone fracture severely impaired the regeneration of muscle that closely contacts the bone fracture site after cold injury. After cold injury, M-cadherin-positive myogenic cells disappeared in the damaged muscle areas of mice receiving the combination of alendronate treatment and bone fracture. The present results suggest that the muscle regeneration capacity is impaired by bone fracture in mice receiving alendronate treatment. The present research on the pharmacological effects of alendronate on muscle regeneration will aid in understanding of the in vivo action of alendronate on skeletal muscles.

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“…These effects seem to be unrelated to the affection of the skeleton [Janssens et al, 2006]. Indeed, a direct pharmacological action on muscle stem cells or myocytes with proliferation of muscle cells or activation of muscle metabolism by alendronate treatment in patients with osteoporosis has been suggested [Harada et al, 2015].…”

mentioning

confidence: 99%

Significant Improvement of Clinical Symptoms, Bone Lesions, and Bone Turnover after Long-Term Zoledronic Acid Treatment in Patients with a Severe Form of Camurati-Engelmann Disease

et al. 2017

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Camurati-Engelmann disease (CED) is an ultrarare autosomal dominant bone dysplasia. Cortical thickening of the diaphyses of the long bones with narrowing of the medullary cavity are associated with bone pain, waddling gait, muscular weakness, easy fatigability, and a marfanoid body habitus. There is no specific treatment for CED. Nonsteroidal anti-inflammatory drugs or glucocorticoids are ineffective in improving bone lesions. A family with a mild to severe form of CED is described. Two patients received long-term bisphosphonate treatment: the 19-year-old female proband was treated with zoledronic acid for 2.2 years; the 4-year-old male proband was treated with neridronic acid for 16 months and with zoledronic acid for an additional 18 months. In both probands, zoledronic acid treatment significantly improved the clinical symptoms, bone lesions, ambulation, and body habitus. Before treatment, both probands showed a marked increase in serum levels of osteocalcin, procollagen type I N-terminal propeptide, and cross-linked carboxyterminal telopeptide of type I collagen, reflecting an increased bone turnover. Bone marker levels returned to their normal values during treatment. Zoledronic acid treatment may be an important therapeutic option in patients with severe CED. Biochemical markers of bone turnover could be considered as surrogate indexes of CED activity.

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Effect of alendronate on muscle mass: Investigation in patients with osteoporosis

Cited by 21 publications

References 27 publications

Preventing muscle wasting by osteoporosis drug alendronate in vitro and in myopathy models via sirtuin‐3 down‐regulation

Preventing muscle wasting by osteoporosis drug alendronate in vitro and in myopathy models via sirtuin‐3 down‐regulation

Impairment of cold injury-induced muscle regeneration in mice receiving a combination of bone fracture and alendronate treatment

Significant Improvement of Clinical Symptoms, Bone Lesions, and Bone Turnover after Long-Term Zoledronic Acid Treatment in Patients with a Severe Form of Camurati-Engelmann Disease

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