Author(s): Sok Kuan Wong 1, Kok-Yong Chin 1, Farihah Hj Suhaimi 2, Fairus Ahmad 2, Soelaiman Ima-Nirwana 1,*
Metabolic syndrome (MetS) is a medical condition characterized by the co-existence of at least three of the following characteristics: central obesity, hyperglycaemia, hypertension, high triglyceride, and low high-density lipoprotein (HDL) cholesterol . Being a multifactorial disease, MetS increases the risk of other diseases, such as cardiovascular disease , non-alcoholic fatty liver disease , type 2 diabetes , and cancer . On the other hand, osteoporosis is a common skeletal disease characterized by low bone mass and deterioration of bone microarchitecture, which increases the risk of fragility fracture . It occurs due to an imbalance in skeletal remodelling process, leading to increased bone resorption and decreased bone formation . Osteoporotic fracture has massive health and economic burdens on the patients and to the healthcare system . Recently, there is a debate concerning whether MetS is associated with osteoporosis. Many studies involving animals and humans have been performed to investigate the relationship between MetS and osteoporosis but the findings were heterogeneous [9-14]. Human observational studies revealed that individual with MetS had either higher [9,12] or lower bone mineral density (BMD) [10,15-17]. Animal studies also yielded inconsistent results, whereby MetS decreased  or had no effect  on BMD in animals.
Bone marrow mesenchymal cells have an equal tendency for adipocytes or osteoblasts differentiation. Stem cells initially proliferate and differentiate into pre-osteoblast, then to mature osteoblast to produce bone matrix . Metabolic syndrome favours adipocytes differentiation and suppresses osteoblasts differentiation, leading to lower bone formation activity . This is evidenced by a lower osteocalcin level in rats fed with high-fat/high-sucrose diet for 27 weeks . Chronic inflammation induced by MetS also increases the formation of osteoclasts and its bone resorptive activities. A previous study by Pirih et al showed high-fat diet elevated circulating carboxyl-terminal telopeptides of type 1 collagen (CTX-1) level, a marker of bone resorption, in hyperlipidaemic mice . The changes in bone cell ratios, surface erosion, mineralization and ultimately microarchitecture due to MetS can be studied using bone histomorphometry methods. Static histomorphometry evaluates the quantity of cells (osteoblast and osteoclast), unmineralized bone (osteoid), and extent of bone resorption (eroded surface). Dynamic histomorphometry studies the changes in cellular activity over time. Structural parameters measure the bone volume and structure, which are the end results of bone remodelling process . However, to the best of our knowledge, the effects of MetS on bone histomorphometric indices are not well-established.
The objective of the current study was to explore the effects of MetS on bone health, in terms of bone mineral content (BMC), BMD, bone histomorphometric indices, and bone remodelling markers, using a MetS rat model. We administered a previously validated high-carbohydrate high-fat (HCHF) diet to the rats to induce MetS . This model is more similar with human dietary pattern causing MetS . We hope that the findings of this study can provide a clear picture on the effects of MetS on changes in the...