Skeletal and mineral metabolic effects of risedronate in a rat model of high-turnover renal osteodystrophy

Ishida, Hiroaki; Komaba, Hirotaka; Hamano, Naoto; Yamato, Hideyuki; Sawada, Kaichiro; Wada, Takehiko; Nakamura, Michio; Fukagawa, Masafumi

doi:10.1007/s00774-020-01095-0

Cited by 11 publications

(8 citation statements)

References 47 publications

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“…The peritrabecular fibrosis has been regarded as the key indicator of high-turnover bone diseases (eg, osteitis fibrosa) when fibroblast-like cells produce much irregularly organized extracellular matrix in response to persistently increased PTH levels. (53) Bone pathologies mediated by hyperparathyroidism and elevated turnover are characterized by active remodeling in both bone formation and resorption. (54) Given the fact that our patient had normal functioning parathyroid and her osteoblastic osteogenesis was low, the histological manifestation in our case seems to be irrelevant.…”

Section: Discussionmentioning

confidence: 99%

Generalized Uncoupled Bone Remodeling Associated With Delayed Healing of Fatigue Fractures

et al. 2022

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Fatigue fractures in bones are common injuries with load-bearing activities, during which the remodeling aimed at removing microdamage has been suggested to play a role in increasing related fracture risk. Much attention has been given to the uncoupling between osteoclastic bone resorption and osteoblastic osteogenesis in fatigue fracture cases; however, the underlying pathophysiologic mechanisms of impaired fracture healing are yet unknown. Here we report multiple fatigue fractures in a physically active woman receiving contraceptive pills for years. Her fracture healing was remarkably slow, although she has been otherwise healthy. The patient underwent bone biopsy of the iliac crest that showed remarkable peritrabecular fibrosis with increased osteoclastic bone resorption combined with relatively low bone formation. Analysis of bone biochemical composition revealed a more complex picture: First, notable declines in bone mineral content-based parameters indicating abnormal mineralization were evident in both cancellous and cortical bone. Second, there was elevation in mineral crystal size, perfection, and collagen maturity in her bone tissues from different anatomical sites. To our knowledge, this is the first report showing generalized uncoupling in bone remodeling, increased peritrabecular fibrosis, and bone compositional changes associated with delayed healing of fatigue fractures. These results may explain delayed healing of fatigue and stress fractures.

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Section: Discussionmentioning

confidence: 99%

Generalized Uncoupled Bone Remodeling Associated With Delayed Healing of Fatigue Fractures

et al. 2022

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“…This concept was supported by a mouse study in which interleukin-1 (IL-1)-induced local bone resorption caused elevations in serum intact FGF23 levels without increasing its mRNA levels, and this elevation in FGF23 was prevented by a pre-treatment with a bisphosphonate pamidronate (39). Similarly, in nephrectomized rats with a high bone turnover renal osteodystrophy, a treatment with a bisphosphonate risedronate suppressed the elevation of serum intact FGF23 levels (40). These findings indicate that the release of FGF23 produced by osteocytes into the circulation is accelerated in association with bone resorption.…”

Section: Local Regulators Of Fgf23 Production In Osteocytesmentioning

confidence: 97%

Roles of osteocytes in phosphate metabolism

Michigami

2022

Front. Endocrinol.

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Osteocytes are dendritic cells in the mineralized bone matrix that descend from osteoblasts. They play critical roles in controlling bone mass through the production of sclerostin, an inhibitor of bone formation, and receptor activator of nuclear factor κ B ligand, an inducer of osteoblastic bone resorption. Osteocytes also govern phosphate homeostasis through the production of fibroblast growth factor 23 (FGF23), which lowers serum phosphate levels by increasing renal phosphate excretion and reducing the synthesis of 1,25-dihydroxyvitamin D (1,25(OH)2D), an active metabolite of vitamin D. The production of FGF23 in osteocytes is regulated by various local and systemic factors. Phosphate-regulating gene homologous to endopeptidase on X chromosome (PHEX), dentin matrix protein 1 (DMP1), and family with sequence similarity 20, member C function as local negative regulators of FGF23 production in osteocytes, and their inactivation causes the overproduction of FGF23 and hypophosphatemia. Sclerostin has been suggested to regulate the production of FGF23, which may link the two functions of osteocytes, namely, the control of bone mass and regulation of phosphate homeostasis. Systemic regulators of FGF23 production include 1,25(OH)2D, phosphate, parathyroid hormone, insulin, iron, and inflammation. Therefore, the regulation of FGF23 in osteocytes is complex and multifactorial. Recent mouse studies have suggested that decreases in serum phosphate levels from youth to adulthood are caused by growth-related increases in FGF23 production by osteocytes, which are associated with the down-regulation of Phex and Dmp1.

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“…In addition to phosphorus binders, vitamin D and its analogs, and calcimimetic agents, other SHPT treatment options include bisphosphonates (drugs inhibiting bone resorption) ( 7 ), synbiotics (combinations of prebiotics and probiotics) ( 45 ), and denosumab (monoclonal antibody) ( 46 ). Denosumab especially is used in patients with inoperable THPT ( 46 ).…”

Section: Treatment For Hptmentioning

confidence: 99%

“…THPT is common in patients with long-term chronic kidney disease, hemodialysis, and kidney transplantation ( 6 ). HPT can cause bone diseases ( 7 ), such as pathological fractures or skeletal deformities, cardiovascular diseases ( 8 ), and kidney stones and may also induce end-stage parathyroid cancer, although this is extremely rare ( 9 , 10 ). Serum intact parathyroid hormone (iPTH) measurement and technetium-99m sestamibi (99mTc-MIBI) parathyroid imaging are the most effective and reliable methods for diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Advances in the treatment of secondary and tertiary hyperparathyroidism

et al. 2022

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Secondary hyperparathyroidism (SHPT) and tertiary hyperparathyroidism (THPT) are common and complicated clinical endocrine diseases. The parathyroid glands maintain endocrine homeostasis by secreting parathyroid hormone to regulate blood calcium levels. However, structural alterations to multiple organs and systems occur throughout the body due to hyperactivity disorder in SHPT and THPT. This not only decreases the patients’ quality of life, but also affects mortality. Since current treatments for these diseases remains unclear, we aimed to develop a comprehensive review of advances in the treatment of SHPT and THPT according to the latest relevant researches.

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Skeletal and mineral metabolic effects of risedronate in a rat model of high-turnover renal osteodystrophy

Cited by 11 publications

References 47 publications

Generalized Uncoupled Bone Remodeling Associated With Delayed Healing of Fatigue Fractures

Generalized Uncoupled Bone Remodeling Associated With Delayed Healing of Fatigue Fractures

Roles of osteocytes in phosphate metabolism

Advances in the treatment of secondary and tertiary hyperparathyroidism

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