Increases in bone marrow fat (BMF) have been associated with skeletal fragility, particularly in obesity and type 2 diabetes. The parathyroid hormone (PTH) is one of the mechanisms that inhibits adipogenesis by acting on the bone marrow mesenchimal stem cells. There have been no study assessing the BMF in conditions of PTH deficiency.
Chronic hypoparathyroidism is a rare disorder characterized by low or undetectable PTH and low serum calcium levels. Bone mineral density (BMD) and bone quality are normal or increased compared to healthy subjects. It is not clear whether these or other features of the hypoparathyroid skeleton could potentially translate into increased skeletal fragility. In this context, the BMF has not been investigated in hypoparathyroidism.
The primary endpoint is to assess BMF and how it could be related with skeletal fragility in hypoparathyroidism. Mechanisms associated with the increase in BMF in the setting of chronic low PTH levels will be explored.
The project will recruit 60 patients with hypoparathyrodism and 60 age and sex-matched healthy subjects. All participants will undergo L1-L4 vertebrae 3 Tesla Magnetic Resonance Imaging to assess the proton density fat fraction; L1-L4, femoral neck, 1/3 radius MD and total body dual X ray absorptiometry (DXA) for BMD and fat and lean mass measurements, and vertebral fracture assessment by DXA. Serum levels of bone tunorver markers, and mineral metabolism parameters will be measured.
Results from the study will comprehensively define for the first time new features of the skeleton in hypoparathyroidism and mechanisms through which they could potentially be associated with skeletal fragility.
The study of BMF in conditions of PTH deficiency will be a completely new research line with the potential of elucidating new mechanisms of PTH action on bone. Additonally, skeletal features of bone in hypoparathyroidism will be better defined, and potentially definitive data will be provided on whether or not there is an increased bone fragility in hypoparathyroidism.
A number of studies have indeed demonstrated that increases in BMF are associated with skeletal fragility. In particular, this association is considered as having a central role in the pathogenesis of skeletal disease associated with obesity and type 2 diabetes. Definition of how these mechanisms could apply to hypoparathyroidism would therefore represent a first step towards the definition of a new metabolic profile of the disease both at the skeletal but potentially also at a systemic level.
The primary hypothesis is that an increase in BMF is one of the unexplored skeletal feature in conditions of PTH deficiency. The lack of PTH is indeed presumably associated with increased adipogenesis in the bone marrow.
Pathways involved in PTH actions on bone marrow will be then evaluated to determine the pathophysiology of the increase in BMF in conditions of PTH deficiency.
Another novelty of the project pertains the hypothesis that the high BMF and not other parameters of bone (such as BMD, bone quality) predisposes to skeletal fragility in hypoparathyroidism. The aspect of a presumed increased fragility in hypoparathyroidism has not be definitely assessed and will be evaluated by the assessment of vertebral fracture in the research project.