Nonalcoholic fatty liver disease and osteoporosis: A potential association with therapeutic implications

Abstract

Nonalcoholic fatty liver disease (NAFLD) and osteoporosis are two highly prevalent metabolic diseases. Increasing experimental evidence supports a pathophysiological link between NAFLD and osteoporosis. A key feature could be chronic, low‐grade inflammation, which characterizes NAFLD and possibly affects bone metabolism. In this context, several factors, including but not limited to receptor activator of nuclear factor kappa‐B ligand, osteoprotegerin, osteopontin and osteocalcin, may serve as mediators. In the clinical setting, most but not all epidemiological evidence indicates that NAFLD is associated with lower bone mineral density or osteoporosis in adults. Although an association between NAFLD and osteoporosis has not yet been established, and thus remains speculative, pharmacological considerations already exist. Some of the current and emerging pharmacological options for NAFLD have shown possible anti‐osteoporotic properties (eg, vitamin E, obeticholic acid, semaglutide), while others (eg, pioglitazone, canagliflozin) have been associated with increased risk of fractures and may be avoided in patients with NAFLD and concomitant osteoporosis, especially those at high fracture risk. Conversely, some anti‐osteoporotic medications (denosumab) might benefit NAFLD, while others (raloxifene) might adversely affect it and, consequently, may be avoided in patients with osteoporosis and NAFLD. If an association between NAFLD and osteoporosis is established, a medication that could target both diseases would be a great advancement. This review summarizes the main experimental and clinical evidence on the potential association between NAFLD and osteoporosis and focuses on treatment considerations derived from this potential association.

Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease

“… 94 However, data from clinical studies currently remain controversial, as elsewhere summarized in detail. 95 Regarding cardiovascular safety, which is a major concern for patients with NAFLD, since cardiovascular diseases represent the first cause of death of NAFLD patients, 86 there are limited data reporting an increase in heart rate and blood pressure after treatment with some FGF-21 analogs, which, however, were not shown by other authors. 96 , 97 The clinical significance of these cardiovascular effects remains to be shown, as well as whether these effects outweigh the above mentioned beneficial effect of FGF-21 analogs on lipid profile, in terms of cardiovascular risk.…”

Osteosarcopenia in NAFLD/MAFLD: An Underappreciated Clinical Problem in Chronic Liver Disease

“…Partial evidence reported that RANKL upregulation could play a key role in NAFLD pathogenesis and be the possible link between hepatic and bone impairment, so its downregulation could be protective for liver health (and bone, too) [ 303 , 304 ]. A suggestive paper reported amelioration of liver function in a woman with NASH and osteoporosis after denosumab administration [ 305 ].…”

Osteoprotegerin deficiency aggravates methionine- choline- deficient diet-induced nonalcoholic steatohepatitis in mice

“…Conversely, as an endocrine organ, bones secret bonederived factors that regulate local bone metabolism and systemic energy metabolic functions. Osteopontin (OPN), irisin, osteocalcin (OCN), and osteoprotegerin (OPG) probably mediate the interactions between bones, adipose tissues, and the liver 7 . Bone-derived factors including OPN and OCN play a role in NAFLD development 8 .…”