Effects of Bisphosphonate Treatment on Circulating Lipid and Glucose Levels in Patients with Metabolic Bone Disorders

Gabriella Iannuzzo,Marco Evangelista,Marco Gentile,Luigi Gennari,Domenico Rendina,Gianpaolo De Filippo,Tommaso Picchioni,Daniela Merlotti,Pasquale Strazzullo,Veronica Abate,Alessio Buonaiuto,Matteo Nicola Dario Di Minno,Alfonso Giaquinto

doi:10.1007/s00223-021-00811-w

Abstract

Bisphosphonates are the first-choice treatment of osteoporosis and Paget’s disease of bone. Among the bisphosphonates, the non-amino-bisphosphonates, such as clodronic acid, are intracellular converted into toxic analogues of ATP and induce cellular apoptosis whereas the amino-bisphosphonates, such as zoledronic acid, inhibit the farnesyl-diphosphate-synthase, an enzyme of the mevalonate pathway. This pathway regulates cholesterol and glucose homeostasis and is a target for statins. In this retrospective cohort study, we evaluated the effects of an intravenous infusion of zoledronic acid (5 mg) or clodronic acid (1500 mg) on blood lipid (i.e. total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglycerides) and glucose levels in patients with osteoporosis and Paget’s disease of bone. All patients were evaluated before, 1 and 6 months after bisphosphonate treatment. Pagetic and osteoporotic patients treated with zoledronic acid showed a significant reduction in glucose and atherogenic lipids during follow-up whereas these phenomena were not observed after clodronic treatment. The effect on circulating lipid levels was similar in naïve and re-treated Pagetic patients. Zoledronic acid treatment was associated with a reduction in blood glucose and atherogenic lipids in patients with metabolic bone disorders. The extent of change was similar to that obtained with the regular assumption of a low-intensity statin. Further studies are warranted to better evaluate the clinical implications of these observations.

Highlights

Atherosclerosis is a leading cause of cardiovascular morbidity and mortality in Western countries and dyslipidemia is one of the most significant risk factors [1]
Age 69.4 ± 9.5 years; body mass index 26.4 ± 2.0 kg/m2, monostotic:polyostotic Paget’s disease of bone (PDB) 41:48), 69 PDB patients treated with clodronic acid (Clo) (PDB-Clo; men:women 38:31, mean age 66.7 ± 10.1 years; body mass index 26.1 ± 2.0 kg/m2, monostotic:polyostotic PDB 31:38) and 47 OP patients treated with zoledronic acid (Zol) (Op-Zol; men:women 5:42, mean age 66.9 ± 10.1 years; body mass index 25.8 ± 1.7 kg/m2) were selected
At T0, Op-Zol patients showed alkaline phosphatase (ALP) levels significantly lower compared to both PDB-Zol and PDB-Clo (p < 0.01, analysis of variance with Bonferroni correction)

Summary

Introduction

Atherosclerosis is a leading cause of cardiovascular morbidity and mortality in Western countries and dyslipidemia is one of the most significant risk factors [1]. Some studies have focused on a possible relationship between metabolic bone disorders (MBDs), cardiovascular diseases (CVDs) and cardiovascular risk factors, primarily dyslipidemia, considering that the incidence and prevalence of MBDs and CVDs are very high in the adult population worldwide [2, 3]. Op affects approximately 200 million people and leads to nearly 9 million fractures annually worldwide [4]. Paget’s disease of bone (PDB) is the second most common MBD after Op worldwide, marked ethnic and geographical variations in its prevalence has been observed [5,6,7,8,9]. PDB is characterized by increased and disorganized bone turnover, which affects one or more skeletal sites, i.e. monostotic and polyostotic PDB, respectively.

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