Endocrine, metabolic, nutritional and body composition abnormalities are common in advanced intensively-treated (transplanted) multiple myeloma

Abstract

Modern treatment strategies have increased life expectancy in multiple myeloma, but little is known about the endocrine, metabolic and nutritional status of long-term survivors. We performed endocrine, metabolic, bone, body composition and nutritional evaluations in 32 patients with intensively-treated, advanced but stable, myeloma a median duration of 6 years from diagnosis and three lines of intensive treatment, including at least one haematopoietic SCT procedure. All patients were off active treatment. There was a high prevalence of endocrine dysfunction: hypothyroidism (9%), hypogonadism (65% males) and elevated prolactin (19%). Adrenocortical function was preserved despite large cumulative corticosteroid pretreatment. Biochemical markers were consistent with postmenopausal status in all females and infertility in males. Nutritionally, 59% were vitamin D insufficient/ deficient, reduced serum folate in 25% and vitamin B12 in 6%. Total body DEXA scanning confirmed 'sarcopenic-obesity' in 65%, but reduced bone density was seen in a minority. We conclude that potentially correctable endocrine, metabolic and nutritional abnormalities are prevalent in heavily-treated patients with stable multiple myeloma. Preservation of bone supports the efficacy of bisphosphonate treatment from diagnosis, but sarcopenic-obesity may contribute to frailty. Ultimately, multi-system screening and appropriate interventions may optimise quality of long-term survival and further studies are warranted.

Adipose, Bone, and Myeloma: Contributions from the Microenvironment

“…This results in the anti-proliferative and anti-tumorigenic effects of adiponectin observed in MM, breast, prostate, colon and liver cancers [74, 78]. Overweight and obese individuals typically present with low levels of adiponectin and are at a greater risk of developing MM when compared to individuals of healthy weight [80, 81]. Mechanistically, deficiency in adiponectin hinders the biological actions of several signaling pathways that are essential to prevent growth, proliferation, migration, and drug resistance of MM cells [81], and adiponectin can alter bone turnover for net bone anabolic or catabolic effects [82, 83].…”

“…Overweight and obese individuals typically present with low levels of adiponectin and are at a greater risk of developing MM when compared to individuals of healthy weight [80, 81]. Mechanistically, deficiency in adiponectin hinders the biological actions of several signaling pathways that are essential to prevent growth, proliferation, migration, and drug resistance of MM cells [81], and adiponectin can alter bone turnover for net bone anabolic or catabolic effects [82, 83]. Hence the net effects of adiponectin on myeloma-induced bone disease and tumor burden remain controversial.…”

“…For example, endocrine, metabolic, nutritional, and body composition abnormalities are common in advanced intensively-treated (transplanted) MM patients; this further complicates the interpretation of the roles of MAT in disease progression and the evaluation of the best treatment approaches [81]. Specifically, intensively treated patients had a high prevalence of endocrine dysfunction (hypothyroidism (9%), hypogonadism (65% males), and elevated prolactin (19%)).…”

“…Specifically, intensively treated patients had a high prevalence of endocrine dysfunction (hypothyroidism (9%), hypogonadism (65% males), and elevated prolactin (19%)). Also, biochemical markers were consistent with post-menopausal status in all females and infertility was high in males and Vitamin D, B12, and folate deficiencies, as well as “sarcopenic-obesity”, were observed in many MM patients [81]. In order to combat the potential that elevated MAT impacts tumor growth in MM, a number of approaches currently exist in the clinic.…”

Metabolic syndrome and cardiovascular disease following hematopoietic cell transplantation: screening and preventive practice recommendations from CIBMTR and EBMT

“…At a median duration of 6 years from diagnosis, dual-X-ray absorptiometry identified sarcopenic obesity in 65% of patients. 39 Importantly, the development of sarcopenic obesity following HCT has yet to be independently associated with increased cardiovascular mortality. In the pediatric population, a cross-sectional study evaluating 54 allo-HCT survivors and 894 healthy participants found a deficiency in lean mass (as identified by dual-X-ray absorptiometry) as compared with fat mass in HCT survivors.…”