Dickkopf-1 negatively regulates the expression of osteoprotegerin, a key osteoclastogenesis inhibitor, by sequestering Lrp6 in primary and metastatic lytic bone lesions

Wang, Jianhang; Zhang, Yuanjin; Li, Hongyan; Liu, Yunyan; Sun, Tao

doi:10.1097/md.0000000000003767

Cited by 9 publications

(5 citation statements)

References 24 publications

(20 reference statements)

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“…In addition to this, a further study found an over-expression of Dkk1 in bone biopsies of lytic lesions from patients with multiple myeloma and metastatic cancers when compared with bone biopsies of patients with primary cancers only. This expression correlated with a decrease in the level of OPG; further increasing the activation of osteoclasts, and so generating a heightened level of bone destruction [11].…”

Section: Introductionmentioning

confidence: 89%

Mechanisms and treatment of bone pain in multiple myeloma

Davies

Fingas

Chantry

2019

Current Opinion in Supportive &Amp; Palliative Care

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Purpose of reviewMultiple myeloma is a haematological malignancy of differentiated B lymphocytes, known as plasma cells. The disease is common in the UK (incidence of 9 cases per 100 000 people) and the most frequent presentation is bone pain caused by skeletal damage. Patients with myeloma also experience neuropathic pain induced by chemotherapy. The management of pain in multiple myeloma is frequently demanding and often sub-optimally addressed. This review seeks to summarize a rational approach to the management of pain experienced by multiple myeloma patients. Recent findingsBone pain has a dramatic detrimental impact on a patient's physical capacity, and therefore, quality of life. Various mechanisms of bone pain have been elucidated; however, neuropathic bone pain in multiple myeloma is not completely understood. Potential mechanisms for this phenomenon; namely increased intraosseous pressure and the acidity of the bone marrow in the disease state will be interrogated. The current analgesic pathways used to treat multiple myeloma bone pain and new advances in therapies that may confer future benefit to patients will briefly be reviewed.

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Section: Introductionmentioning

confidence: 89%

Mechanisms and treatment of bone pain in multiple myeloma

Davies

Fingas

Chantry

2019

Current Opinion in Supportive &Amp; Palliative Care

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“…В биоптатах, полученных из очагов остеолизиса у пациентов с ММ и метастатическими солидными опухолями, была обнаружена гиперэкспрессия Dkk1. Степень экспрессии этого белка коррелировала со снижением концентрации OPG, активацией остеокластов и степенью остеодеструкции [16].…”

Section: поддерживающая терапияunclassified

Pathophysiology and treatment of pain in multiple myeloma

Semochkin

2023

Medicinskij sovet

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Most patients with multiple myeloma (MM) suffer from chronic pain of varying degrees of intensity at every stage of the natural disease process. Osteolytic bone lesions are one of the most common complications of MM. The bone disease visualized by PET/CT and MRI affects up to 90% of newly diagnosed MM patients, increasing the risk of the development of skeletal-related events. Pathological fractures and spinal cord compression occur in 17% and 6% of patients, respectively. Bone pain is explained by an increase in pressure in the bone marrow, the release of chemical mediators by myeloma plasma cells, and the occurrence of microcracks in the bones, indirectly to a violation of local metabolism. Management of myeloma bone disease includes anti-myeloma chemotherapy and radiotherapy, antiresorptive therapy with bisphosphonates or denosumab, and direct pharmacological pain correction. Patients with pathological vertebral fractures and without spinal cord compression should be considered for vertebroplasty or kyphoplasty. The use of proteasome inhibitors and monoclonal antibodies for the treatment of MM is associated with a risk of herpes simplex virus (HSV) and varicella-zoster virus (VZV) reactivation. The result of the healing of herpetic eruptions in some patients will be the development of postherpetic neuralgia, manifested by excruciating pain for months or years. Moreover, the treatment with proteasome inhibitor bortezomib is often associated with the development of long-term persistent peripheral neuropathy, often complicated by pain. According to their neurobiological and clinical features, pain is classified into nociceptive, neuropathic, and functional. Bone pain is nociceptive and for postherpetic and chemotherapy-induced neuropathy, the neuropathic component is more significant. Opioids are the drugs of choice for moderate to severe nociceptive pain, while anticonvulsants and antidepressants are the most commonly used adjuvants for neuropathic pain. This review summarizes information on the pathophysiology of various types of pain syndrome in patients with MM, as well as on modern approaches to the prevention and treatment of complications. The issues of the pharmacology of opioid analgesics are discussed. The review concludes with data from a clinical trial of a new domestic non-opioid μ1-opioid receptor agonist Tafalgin, considered a real alternative to narcotic analgesics.

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“…In the presence of sclerostin, DKK-1 decreases β-catenin, which reduces differentiation of osteoblasts. (37,110) A humanized immunoglobulin G (IgG) anti-DKK-1 monoclonal antibody, BHQ880, has been evaluated in vitro and in vivo. (111) BHQ880 was successful at reversing the inhibiting effect of DKK-1 on osteoblast differentiation and promoted bone formation in a murine model of human MM.…”

Section: Anti-dkk-1mentioning

confidence: 99%