Reductions in degree of mineralization and enzymatic collagen cross-links and increases in glycation-induced pentosidine in the femoral neck cortex in cases of femoral neck fracture

Saito, Mitsuru; Fujii, Katsuyuki; Soshi, Shigeru; Tanaka, Takaaki

doi:10.1007/s00198-006-0087-0

Cited by 211 publications

(143 citation statements)

References 56 publications

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“…Its accumulation is associated with age-related degradation in the mechanical properties of bone (17,23). Pentosidine levels are higher in the bones of patients with femoral neck fractures compared with age-matched controls (24,25). Serum pentosidine concentrations were positively correlated with the radiographic severity of lumbar spondylosis in a crosssectional study involving Japanese subjects (26).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Bone Turnover / Quality Markers and Bone Mineral Density in Prostate Cancer Patients Receiving Androgen Deprivation Therapy with or without Denosumab

Miyazawa

Sekine

Syuto

et al. 2017

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Abstract. Background/Aim: Androgen deprivation therapy (ADT) is a mainstay therapy for prostate cancer (PCa). ADT induces bone loss and increases the risk of osteoporosis and fractures. Recently, loss of bone quality has received attention as a factor that causes loss of bone strength independent of bone mineral density (BMDProstate cancer (PCa) is the most common cancer in males in Western countries and its incidence has increased in Japan (1). Androgen deprivation therapy (ADT) with gonadotropinreleasing hormone (GnRH) agonists, GnRH antagonists or bilateral orchiectomy is a well-established treatment for advanced PCa (2). ADT is also used to manage cases of localized PCa when radical treatment cannot be administered (3). The administration of ADT improves disease-free survival and overall survival in men with locally advanced PCa treated with radiation therapy (4). ADT functions by decreasing testosterone to castrate levels. ADT also markedly decreases serum estradiol levels because estradiol is derived from the peripheral conversion of testosterone by aromatase, also called estrogen synthase. Therefore, side-effects associated with estrogen deficiency are also observed. Estradiol plays a role in bone formation and bone resorption in men (5). Therefore, ADT decreases bone mineral density (BMD) and increases the incidence of clinical fractures (6, 7). The risk of fracture increases with an increasing duration of ADT (6, 7). Patients with prostate carcinoma bone metastases are faced with the risk of skeletal complications, including pathologic fractures, which are collectively termed skeletal-related events (SREs) (8). SREs are associated with mortality, increased pain, decreased quality of life and increased treatment costs (9).Although several drugs, including bisphosphonates and selective estrogen-receptor modulators, can prevent a decreased BMD, clinical trials of those drugs have revealed that the effects on fracture prevention are insufficient (10, 11). In contrast, denosumab was found to increase BMD at all sites and decrease the incidence of new vertebral fractures among men receiving ADT for non-metastatic PCa (12). Furthermore, denosumab decreased the risk of skeletal complications compared to zoledronic acid in castrationresistant prostate cancer (CRPC) patients with bone metastases (13). The administration of denosumab decreased the serum levels of bone turnover markers (BTMs), including type-1 C-teropeptide (sCTX) and tartrate-resistant alkaline phosphatase 5b (TRAP-5b) compared to placebo (14). Therefore, BTMs are often used to predict the effects of denosumab during CRPC patient care.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Bone Turnover / Quality Markers and Bone Mineral Density in Prostate Cancer Patients Receiving Androgen Deprivation Therapy with or without Denosumab

Miyazawa

Sekine

Syuto

et al. 2017

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“…Several prior studies found that higher levels of AGEs are associated with decreased postyield properties of cortical and trabecular bone. 23,24,29,58 Moreover, in trabecular bone from human femora, Tang et al 27 reported a negative relationship between PEN and postyield mechanical properties, but no association with preyield properties. We did not evaluate postyield properties in this study because they are problematic for compression tests since the trabecular bone compresses upon itself, thus our finding that PEN was not associated with mechanical properties is consistent with previous studies.…”

Section: Discussionmentioning

confidence: 99%

Effects of preexisting microdamage, collagen cross‐links, degree of mineralization, age, and architecture on compressive mechanical properties of elderly human vertebral trabecular bone

Follet

Viguet-Carrin

Burt‐Pichat

et al. 2010

Journal Orthopaedic Research

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Previous studies have shown that the mechanical properties of trabecular bone are determined by bone volume fraction (BV/ TV) and microarchitecture. The purpose of this study was to explore other possible determinants of the mechanical properties of vertebral trabecular bone, namely collagen cross-link content, microdamage, and mineralization. Trabecular bone cores were collected from human L2 vertebrae (n ¼ 49) from recently deceased donors 54-95 years of age (21 men and 27 women). Two trabecular cores were obtained from each vertebra, one for preexisting microdamage and mineralization measurements, and one for BV/TV and quasi-static compression tests. Collagen cross-link content (PYD, DPD, and PEN) was measured on surrounding trabecular bone. Advancing age was associated with impaired mechanical properties, and with increased microdamage, even after adjustment by BV/TV. BV/TV was the strongest determinant of elastic modulus and ultimate strength (r 2 ¼ 0.44 and 0.55, respectively). Microdamage, mineralization parameters, and collagen cross-link content were not associated with mechanical properties. These data indicate that the compressive strength of human vertebral trabecular bone is primarily determined by the amount of trabecular bone, and notably unaffected by normal variation in other factors, such as crosslink profile, microdamage and mineralization. Keywords: bone strength; microdamage; microarchitecture; mineralization; collagen cross-links; vertebral trabecular bone Several studies have shown that the mechanical properties of trabecular bone are influenced by bone volume fraction (BV/TV) and microarchitecture. 1,2 However, additional factors, such as degree of mineralization, preexisting microdamage, and collagen cross-link profile may also play a role, yet the contribution of these factors to human trabecular bone mechanical properties remains incompletely understood.Increased mineralization of cortical bone is exponentially related to increased stiffness, but decreased energy absorption. 3 A similar trend was seen in human trabecular bone from the calcaneus, with a positive relationship between mineralization and elastic modulus, after adjusting for BV/TV. 4 It has also been suggested that a reduction in the heterogeneity of mineralization density distribution leads to increased bone fragility, 5 but there are few data to support this assertion.Microdamage has been largely studied in animal models and in human cortical bone, with only a few studies reporting microdamage in human trabecular bone either naturally occurring 6-11 or due to loading ex-vivo. 12 In cortical bone, microdamage accumulation leads to decreased mechanical properties, 13,14 and therefore has been implicated in skeletal fragility and stress fractures. 15 However, the association between microdamage and cortical bone fracture toughness was weak, 16 raising questions as to the role of microdamage in cortical bone. Increased microdamage has also been associated with decreased strength in human vertebral cancellous bone; 1...

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“…In human, osteoporotic bones, which exhibit decreased quantity and impaired mineralization of bone, have shown lower content of collagen 18,19) and higher extent of Lys hydroxylation [19][20][21][22] be partly damaged compared to those from fresh bone. However, the contents of collagen (average of 125~128 ìg/mg of dried bone)…”

Section: Discussionmentioning

confidence: 99%

Higher Contents of Mineral and Collagen but Lower of Hydroxylysine of Collagen in Mandibular Bone Compared with Those of Humeral and Femoral Bones in Human

Sasaki

Mizutani

Katafuchi

et al. 2010

J. Hard Tissue Biology.

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Minerals and collagen are major components of bone. At present, little is known about the material property of the jaw bone compared to other bones of the body. The purpose of this study was to characterize the material property of mandibular bone expressed by the amount of mineral, collagen, and hydroxylysine (Hyl) in comparison with humeral and femoral bones using human cadavers. Mineral and collagen contents were significantly higher in the mandible than in humerus and femur but Hyl was significantly lower in the mandible. Among the three indices, a weak but significantly positive correlation between collagen and mineral contents was observed. On the contrary, Hyl showed a weak but significantly negative correlation with mineral. The three indices were almost not affected by aging, gender, and dental status which were thought to influence bone quantity. These results suggest that human mandibular bone differs in material property from humeral and femoral bones, and may possess a higher mechanical property explained by the hypothesis that adequate and no excessive extent of lysine hydroxylation of collagen leads to optimal collagen fibrillogenesis and matrix mineralization. The assessment of bone property as shown in this study could disclose unknown characteristics which cannot be expressed by bone quantity.

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Reductions in degree of mineralization and enzymatic collagen cross-links and increases in glycation-induced pentosidine in the femoral neck cortex in cases of femoral neck fracture

Abstract: These results suggest that reductions in the degree of mineralization and enzymatic cross-links and excessive formation of pentosidine may play an important role in explaining poor bone quality in osteoporosis.

Cited by 211 publications

References 56 publications

Evaluation of Bone Turnover / Quality Markers and Bone Mineral Density in Prostate Cancer Patients Receiving Androgen Deprivation Therapy with or without Denosumab

Evaluation of Bone Turnover / Quality Markers and Bone Mineral Density in Prostate Cancer Patients Receiving Androgen Deprivation Therapy with or without Denosumab

Effects of preexisting microdamage, collagen cross‐links, degree of mineralization, age, and architecture on compressive mechanical properties of elderly human vertebral trabecular bone

Higher Contents of Mineral and Collagen but Lower of Hydroxylysine of Collagen in Mandibular Bone Compared with Those of Humeral and Femoral Bones in Human

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