Skeletal-related events significantly impact health-related quality of life in metastatic castration-resistant prostate cancer: data from PREVAIL and AFFIRM trials

Saad, Fred; Ivanescu, Cristina; Phung, De; Loriot, Yohann; Abhyankar, Sarang; Beer, Tomasz M.; Tombal, Bertrand; Holmström, Stefan

doi:10.1038/pcan.2016.62

Cited by 50 publications

(32 citation statements)

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“…These events can have a negative impact on morbidity, ability to work, and social activity. [41][42][43] Furthermore, fractures and other skeletal complications can place a considerable burden on health care resources. 44…”

Section: Part 1 Rationale For Treatment With Bisphosphonates or Denosmentioning

confidence: 99%

Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment

Nicolatou‐Galitis

Schiødt

Mendes

et al. 2019

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

251

203

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Skeletal complications caused by osteoporosis or bone metastases are associated with considerable pain, increased mortality, and reduced quality of life. Furthermore, such events place a burden on health care resources. Agents that prevent bone resorption, such as bisphosphonates or denosumab, can reduce the risk of skeletal-related events and are widely used in patients with osteoporosis or bone metastases of cancer. Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but potentially serious, adverse event associated with high cumulative doses of bisphosphonates or denosumab. However, MRONJ can be treated, and the likelihood of the development of this condition can be reduced through prophylactic dental care and the maintenance of good oral hygiene. Dentists, as part of a multiprofessional team, have a critical role in preventing MRONJ. This review describes the incidence and pathophysiology of MRONJ and provides guidance for dental practitioners with regard to the screening, prophylactic treatment, diagnosis, and management of patients with this condition. (Oral Surg Oral Med Oral Pathol Oral Radiol 2019;127:117À135) Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon condition that can occur after exposure to agents used to prevent bone complications, such as bisphosphonates or denosumab, or treatment with other agents, such as angiogenesis inhibitors. 1 In the majority of cases, MRONJ manifests as exposed bone in the maxillofacial region (Figure 1), although non-exposed MRONJ has also been recognized (Figure 2). 2-5 Bisphosphonates and denosumab are predominantly used to reduce the risk of skeletal complications in patients with bone loss, resulting from long-term cancer treatment or osteoporosis, and in patients with malignant bone disease. 6-8 Bisphosphonates are small molecules that dock in hydroxyapatite-binding sites on bone surfaces. When osteoclasts begin to resorb bisphosphonate-impregnated bone, the liberated bisphosphonates bind to farnesyl pyrophosphate synthase inside the osteoclasts, ultimately leading to apoptosis. 8-10 Denosumab is a fully human monoclonal antibody, which has a different mode of action from that of bisphosphonates. It targets and binds to the receptor activator of nuclear factor k-B (RANK) ligand (RANKL); in doing so it prevents the activation of RANK on the surface of osteoclasts and osteoclast precursors. Inhibition of the RANKLÀRANK interaction impedes osteoclast formation, function, and survival, thereby decreasing bone resorption. 11 MRONJ is more prevalent among patients receiving high cumulative doses of bisphosphonates or denosumab than in patients who receive lower doses. 12,13 The first cases Statement of Clinical Relevance Medication-related osteonecrosis of the jaw is a rare, but potentially serious, complication of treatment with bisphosphonates and denosumab. It is important for dentists to be aware of ways to identify and treat patients at risk of this condition.

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Section: Part 1 Rationale For Treatment With Bisphosphonates or Denosmentioning

confidence: 99%

Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment

Nicolatou‐Galitis

Schiødt

Mendes

et al. 2019

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

251

203

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“…Cancers including breast, prostate and lung cancer show a strong predilection for spreading to bone to develop bone metastases (1)(2)(3). Cancer metastasis to bone is associated with debilitating and life-limiting skeletal complications such as pathological fracture and spinal cord compression (4)(5)(6). In addition, bone pain is also one of the most common and devastating complications of bone metastasis and more than 70% of advanced cancer patients with bone metastases suffer from bone pain (4,(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Decreased sensory nerve excitation and bone pain associated with mouse Lewis lung cancer in TRPV1-deficient mice

et al. 2017

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Bone pain is one of the most common and life-limiting complications of cancer metastasis to bone. Although the mechanism of bone pain still remains poorly understood, bone pain is evoked as a consequence of sensitization and excitation of sensory nerves (SNs) innervating bone by noxious stimuli produced in the microenvironment of bone metastases. We showed that bone is innervated by calcitonin gene-related protein (CGRP) SNs extending from dorsal root ganglia (DRG), the cell body of SNs, in mice. Mice intratibially injected with Lewis lung cancer (LLC) cells showed progressive bone pain evaluated by mechanical allodynia and flinching with increased CGRP SNs in bone and augmented SN excitation in DRG as indicated by elevated numbers of pERK- and pCREB-immunoreactive neurons. Immunohistochemical examination of LLC-injected bone revealed that the tumor microenvironment is acidic. Bafilomycin A1, a selective inhibitor of H secretion from vacuolar proton pump, significantly alleviated bone pain, indicating that the acidic microenvironment contributes to bone pain. We then determined whether the transient receptor potential vanilloid 1 (TRPV1), a major acid-sensing nociceptor predominantly expressed on SNs, plays a role in bone pain by intratibially injecting LLC cells in TRPV1-deficient mice. Bone pain and SN excitation in the DRG and spinal dorsal horn were significantly decreased in TRPV1 mice compared with wild-type mice. Our results suggest that TRPV1 activation on SNs innervating bone by the acidic cancer microenvironment in bone contributes to SN activation and bone pain. Targeting acid-activated TRPV1 is a potential therapeutic approach to cancer-induced bone pain.

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“…Bone metastases are associated with SREs, such as pathological fracture, spinal cord compression, and surgical or radiation intervention of the bone. SREs are known to increase morbidity and to negatively impact QoL [9]. The aim of treatment for SREs is focused on delaying the onset of adverse events and maintaining QoL and functional status in patients with bone metastatic PCa [10].…”

Section: Pathophysiology Underlying Prostate Cancer Bone Metastasismentioning

confidence: 99%

Pathophysiology of Bone Loss in Patients with Prostate Cancer Receiving Androgen-Deprivation Therapy and Lifestyle Modifications for the Management of Bone Health: A Comprehensive Review

Kim

Koo

2020

Cancers

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Androgen-deprivation therapy (ADT) is a systemic therapy administered for the management of advanced prostate cancer (PCa). Although ADT may improve survival, long-term use reduces bone mass density (BMD), posing an increased risk of fracture. Considering the long natural history of PCa, it is essential to preserve bone health and quality-of-life in patients on long-term ADT. As an alternative to pharmacological interventions targeted at preserving BMD, current evidence recommends lifestyle modifications, including individualized exercise and nutritional interventions. Exercise interventions include resistance training, aerobic exercise, and weight-bearing impact exercise, and have shown efficacy in preserving BMD. At the same time, it is important to take into account that PCa is a progressive and debilitating disease in which a substantial proportion of patients on long-term ADT are older individuals who harbor axial bone metastases. Smoking cessation and limited alcohol consumption are commonly recommended lifestyle measures in patients receiving ADT. Contemporary guidelines regarding lifestyle modifications vary by country, organization, and expert opinion. This comprehensive review will provide an evidence-based, updated summary of lifestyle interventions that could be implemented to preserve bone health and maintain quality-of-life throughout the disease course of PCa.

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Skeletal-related events significantly impact health-related quality of life in metastatic castration-resistant prostate cancer: data from PREVAIL and AFFIRM trials

Cited by 50 publications

References 28 publications

Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment

Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment

Decreased sensory nerve excitation and bone pain associated with mouse Lewis lung cancer in TRPV1-deficient mice

Pathophysiology of Bone Loss in Patients with Prostate Cancer Receiving Androgen-Deprivation Therapy and Lifestyle Modifications for the Management of Bone Health: A Comprehensive Review

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