Reviewing the Significance of Vitamin D Substitution in Monoclonal Gammopathies

Abstract

Vitamin D is a steroid hormone that is essential for bone mineral metabolism and it has several other effects in the body, including anti-cancer actions. Vitamin D causes a reduction in cell growth by interrupting the cell cycle. Moreover, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, exerts various effects via its interaction with the vitamin D receptor on the innate and adaptive immune system, which could be relevant in the onset of tumors. Multiple myeloma is a treatable but incurable malignancy characterized by the growth of clonal plasma cells in protective niches in the bone marrow. In patients affected by multiple myeloma, vitamin D deficiency is commonly correlated with an advanced stage of the disease, greater risk of progression, the development of pathological fractures, and a worse prognosis. Changes in the vitamin D receptor often contribute to the occurrence and progress of deficiencies, which can be overcome by supplementation with vitamin D or analogues. However, in spite of the findings available in the literature, there is no clear standard of care and clinical practice varies. Further research is needed to better understand how vitamin D influences outcomes in patients with monoclonal gammopathies.

The Global Prevalence of Vitamin D Deficiency and Insufficiency in Patients with Multiple Myeloma: A Systematic Review and Meta-Analysis

“…The clinical significance of vitamin D and its metabolites in patients with MM is attributed to their participation in the regulation of calcium homeostasis and bone metabolism [ 24 ]. Vitamin D deficiency and insufficiency have been observed to cause a direct and erosive degradation of bone tissues, which is characterized by the manifestation of typical osteoclast markers, such as the formation of osteoclasts [ 69 , 70 ].…”

“…Patients with MGUS experience a 1.4–1.7 times greater occurrence of skeletal fractures [ 22 ], with a particular emphasis on vertebral fractures [ 23 ]. The deficiency of vitamin D facilitates the advancement of MGUS and SMM to MM by stimulating osteoclasts and enhancing osteoclastogenesis via the generation of various cytokines and molecules that possess the capability of osteoclast-activating factors (OAF) [ 24 ], including but not limited to interleukin-6 (IL-6), IL-1β, and IL-3 when interacting with the bone microenvironment [ 25 ]. The insufficiency of vitamin D may considerably augment the likelihood of advancement from a premalignant antecedent to MM.…”

“…Additionally, vitamin D has been demonstrated to exhibit anti-inflammatory effects by reducing the production of pro-inflammatory cytokines and increasing the production of anti-inflammatory cytokines, leading to the modification of the microenvironment in cases of MM [ 30 ]. A number of studies indicate that vitamin D may possess antiproliferative properties against MM cells due to its regulation of cell cycle progression, induction of apoptosis, and inhibition of angiogenesis [ 24 ].…”

Protective Effects of High-Density Lipoprotein on Cancer Risk: Focus on Multiple Myeloma

“…Due to HDL’s suppression during vitamin D deficiency, previous studies have linked low HDL levels to this condition [ 172 , 173 ]. A vitamin D deficit is frequently associated with an advanced stage of MM, an increased risk of progression, the development of pathological fractures, and a poorer prognosis [ 174 ]. Additionally, there is growing evidence, derived from both in vitro research and clinical trials, that vitamin D supplementation may be advantageous for patients with multiple myeloma as an adjuvant treatment.…”

The Anti-Cancer Effect of Cinnamon Aqueous Extract: A Focus on Hematological Malignancies

“…The use of medical plants has been demonstrated to be useful in hematological malignancies, and this fact is undoubtedly arousing because every day clinicians in hematology and oncology units are confronted with the adverse effects of traditional drugs, which can sometimes cause the stop of the treatment if it is intolerable for patients and dangerous for their health [ 57 , 58 , 59 , 60 , 61 ]. Scientific research showed the efficacy of different natural compounds both in the prevention and cure of cancer [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ].…”