Clinical Disorders of Bone Resorption

Russell, Graham; Mueller, Gabrielle; Shipman, C M; Croucher, Peter I.

doi:10.1002/0470846658.ch17

Cited by 30 publications

(14 citation statements)

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“…A major comorbidity in RA patients is a generalized skeletal BMD reduction and microarchitectural deterioration. (6)(7)(8) RA patients versus non-RA patients show a 22.1% increased incidence of osteoporosis and 11.4% BMD reduction, whereas the overall frequency of osteoporosis and BMD below the expected age range in RA subjects versus non-RA subjects was 1.9 and 7.8 times higher, respectively. (9) Nitrogen-containing bisphosphonates (BPs), strong inhibitors of osteoclastic bone resorption, are widely used to manage bone diseases such as osteoporosis (10) or bone malignancy.…”

Section: Introductionmentioning

confidence: 87%

“…A major comorbidity in RA patients is a generalized skeletal BMD reduction and microarchitectural deterioration . RA patients versus non‐RA patients show a 22.1% increased incidence of osteoporosis and 11.4% BMD reduction, whereas the overall frequency of osteoporosis and BMD below the expected age range in RA subjects versus non‐RA subjects was 1.9 and 7.8 times higher, respectively …”

Section: Introductionmentioning

confidence: 99%

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Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in Mice. A Randomized, Prospective, Controlled Animal Study

Molon

Hsu

Bezouglaia

et al. 2016

Journal of Bone and Mineral Research

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Rheumatoid arthritis (RA), an autoimmune inflammatory disorder, results in persistent synovitis with severe bone and cartilage destruction. Bisphosphonates (BPs) are often utilized in RA patients to reduce bone destruction and manage osteoporosis. However, BPs, especially at high doses, are associated with osteonecrosis of the jaw (ONJ). Here, utilizing previously published ONJ animal models, we are exploring interactions between RA and ONJ incidence and severity. DBA1/J-mice were divided in 4 groups: control, zoledronic acid (ZA), collagen induced arthritis (CIA), and CIA-ZA. Animals were pre-treated with vehicle or ZA. Bovine collagen II emulsified in Freund’s adjuvant was injected to induce arthritis (CIA) and the mandibular molar crowns were drilled to induce periapical disease. Vehicle or ZA treatment continued for 8-weeks. ONJ indices were measured by micro-CT and histological examination of maxillae and mandibles. Arthritis development was assessed by visual scoring of paw swelling, and by micro-CT and histology of interphalangeal and knee joints. Maxillae and mandibles of control and CIA mice showed bone loss, PDL space widening, lamina dura loss and cortex thinning. ZA prevented theses changes in both ZA and CIA-ZA groups. Epithelial to alveolar crest distance was increased in the control and CIA mice. This distance was preserved in ZA and CIA-ZA animals. Empty osteocytic lacunae and areas of osteonecrosis were present in ZA and CIA-ZA but more extensively in CIA-ZA animals, indicating more severe ONJ. CIA and CIA-ZA groups developed severe arthritis in the paws and knees. Interphalangeal and knee joints of CIA mice showed advanced bone destruction with cortical erosions and trabecular bone loss, and ZA treatment reduced these effects. Importantly, no osteonecrosis was noted adjacent to areas of articular inflammation in CIA-ZA mice. Our data suggest that ONJ burden was more pronounced in ZA treated CIA mice and that RA could be a risk factor for ONJ development.

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Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in Mice. A Randomized, Prospective, Controlled Animal Study

Molon

Hsu

Bezouglaia

et al. 2016

Journal of Bone and Mineral Research

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“…Bone integrity is maintained by the remodeling activity of boneresorbing osteoclasts and bone-generating osteoblasts [57]. Bone remodeling can release growth factors from the bone matrix, promoting the development of metastasis by stimulating the proliferation of dormant cancer cells.…”

Section: Stem Cell Niche and The Bone Marrow Microenvironmentmentioning

confidence: 99%

“…Nitrogen-containing bisphosphonates (N-BPs) are antiresorptive agents that attach to the mineralized bone matrix with high affinity and are ingested by osteoclasts during osteolysis [57]. Once internalized, N-BPs inhibit the mevalonate pathway in osteoclasts, which is the known mechanism of action for this bone-resorbing activity [1].…”

Section: Interrupting Communication Between Tumor Cells and Bonementioning

confidence: 99%

Relevance of Micrometastases and Targeting the Bone Marrow Niche with Zoledronic Acid in Breast Cancer

Aft¹

2012

CCTR

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During the course of cancer metastasis development, invasive tumor cells circulate through the blood stream and disseminate to other tissues. Circulating and disseminated tumor cells (CTCs and DTCs, respectively) may be the source of local and distant metastases and are a promising target for anticancer therapy. Multiple studies have shown that the detection of DTCs or CTCs correlates with increased risk of disease recurrence, suggesting that reducing the prevalence and persistence of these cells is clinically relevant. The development of metastases is a multistep process that involves complex biologic processes and a multitude of growth factors. The bone marrow provides a portion of these growth factors and a nutrient-rich microenvironment in which dormant cancer cells can survive and transition to metastasis-initiating cells. The molecular interactions between DTCs and the bone marrow microenvironment enable DTCs to evade cytotoxic chemotherapy, allowing them to lie dormant for extended periods of time before becoming active and metastasizing to secondary sites. Alteration of the bone marrow microenvironment with antiresorptive agents, such as bisphosphonates, may render the bone marrow less suitable for cancer cell growth, possibly interfering with the metastatic cascade. Clinical studies have shown that the nitrogen-containing bisphosphonate zoledronic acid can reduce the persistence and prevalence of DTCs in patients with breast cancer, suggesting that zoledronic acid may improve clinical outcomes. Targeting the metastatic niche by altering the microenvironment in the bone marrow may be an effective anticancer strategy.

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“…PTH stimulates bone resorption by promoting an increase in the number of actively resorbing osteoclasts and regulation of tumor necrosis factor (TNF) ligand families as osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL) [9]. Osteoblastic cells express a cell surface protein (RANKL) which binds to its receptor RANK on osteoclasts [10] leading to stimulation of osteoclasts differentiation and also stimulates osteoblastic cells to secrete OPG which acts as decoy receptor for RANKL and inhibits osteoclasts differentiation [11]. It was found that in diabetic rats there is a two fold increase in RANKL and tumor necrosis factor a levels, which is associated with increased resorption of bones [12].…”

Section: Introductionmentioning

confidence: 99%

Modulatory effects of l-arginine and soy enriched diet on bone homeostasis abnormalities in streptozotocin-induced diabetic rats

El-Maraghy

Mehana

2015

Chemico-Biological Interactions

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Clinical Disorders of Bone Resorption

Cited by 30 publications

References 0 publications

Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in Mice. A Randomized, Prospective, Controlled Animal Study

Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in Mice. A Randomized, Prospective, Controlled Animal Study

Relevance of Micrometastases and Targeting the Bone Marrow Niche with Zoledronic Acid in Breast Cancer

Modulatory effects of l-arginine and soy enriched diet on bone homeostasis abnormalities in streptozotocin-induced diabetic rats

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