Farihah Suhaimi

Effects of calcium supplements on fracture healing in a rat osteoporotic model

Fracture healing is a complex process, which is further complicated if the bone is osteoporotic. Calcium is one of the important minerals in bone and has been found to prevent osteoporosis but its role in fracture healing of osteoporotic bone is still unclear. We carried out a study on the effects of calcium supplementation on the late phase healing of fractured osteoporotic bone using an ovariectomized rat model. Twenty‐four female Sprague–Dawley rats were divided into three groups: sham‐operated (SO), ovariectomized‐control (OVXC), and ovariectomized + calcium supplements (Ca). The right femurs of all the rats were fractured at mid‐epiphysis and a K‐wire was inserted for internal fixation. After 2 months of treatment, the rats were sacrificed and the femora were dissected out for radiological and biomechanical assessment. As expected, osteoporosis resulted in impaired healing as shown by the poor radiological and biomechanical properties of the OVXC group. CT scans showed significantly lower callus volumes in the SO and Ca groups compared to the OVXC group. Radiological scoring of fracture healing and callus staging of the SO and Ca groups were better than the OVXC group. However, the biomechanical parameters of the Ca group were significantly lower than the SO group and similar to the OVXC group. Therefore, calcium supplements may appear to improve fracture healing of osteoporotic bone but failed to improve strength.

Animal models of metabolic syndrome: a review

Metabolic syndrome (MetS) consists of several medical conditions that collectively predict the risk for cardiovascular disease better than the sum of individual conditions. The risk of developing MetS in human depends on synergy of both genetic and environmental factors. Being a multifactorial condition with alarming rate of prevalence nowadays, establishment of appropriate experimental animal models mimicking the disease state in humans is crucial in order to solve the difficulties in evaluating the pathophysiology of MetS in human. This review aims to summarize the underlying mechanisms involved in the pathophysiology of dietary, genetic, and pharmacological models of MetS. Furthermore, we will discuss the usefulness, suitability, pros and cons of these animal models. Even though numerous animal models of MetS have been established, further investigations on the invention of new animal model and clarification of plausible mechanisms are still necessary to confer a better understanding to researchers on the selection of animal models for their studies.

The Relationship between Metabolic Syndrome and Osteoporosis: A Review

Metabolic syndrome (MetS) and osteoporosis are two major healthcare problems worldwide. Metabolic syndrome is a constellation of medical conditions consisting of central obesity, hyperglycemia, hypertension, and dyslipidemia, in which each acts on bone tissue in different ways. The growing prevalence of MetS and osteoporosis in the population along with the controversial findings on the relationship between both conditions suggest the importance for further investigation and discussion on this topic. This review aims to assess the available evidence on the effects of each component of MetS on bone metabolism from the conventional to the contemporary. Previous studies suggested that the two conditions shared some common underlying pathways, which include regulation of calcium homeostasis, receptor activator of NF-κB ligand (RANKL)/receptor activator of the NF-κB (RANK)/osteoprotegerin (OPG) and Wnt-β-catenin signaling pathways. In conclusion, we suggest that MetS may have a potential role in developing osteoporosis and more studies are necessary to further prove this hypothesis.

Nigella sativa: A Potential Antiosteoporotic Agent

Nigella sativa seeds (NS) has been used traditionally for various illnesses. The most abundant and active component of NS is thymoquinone (TQ). Animal studies have shown that NS and TQ may be used for the treatment of diabetes-induced osteoporosis and for the promotion of fracture healing. The mechanism involved is unclear, but it was postulated that the antioxidative, and anti-inflammatory activities may play some roles in the treatment of osteoporosis as this bone disease has been linked to oxidative stress and inflammation. This paper highlights studies on the antiosteoporotic effects of NS and TQ, the mechanisms behind these effects and their safety profiles. NS and TQ were shown to inhibit inflammatory cytokines such as interleukin-1 and 6 and the transcription factor, nuclear factor κB. NS and TQ were found to be safe at the current dosage for supplementation in human with precautions in children and pregnant women. Both NS and TQ have shown potential as antiosteoporotic agent but more animal and clinical studies are required to further assess their antiosteoporotic efficacies.

Expression of TGF-β1 in the blood during fracture repair in an estrogen-deficient rat model

OBJECTIVES: Previous studies have reported that osteoporosis due to estrogen deficiency influences fracture healing. Transforming growth factor (TGF-β) has been found to be involved in fracture healing via the regulation of the differentiation and activation of osteoblasts and osteoclasts. The current study aimed to determine the effects of estrogen on the expression of TGF-β1 during fracture healing in ovariectomized rats. METHODS: Thirty female Sprague-Dawley rats weighing 200–250 g were assigned to: (i) a sham-operated group that was given a normal saline; (ii) an ovariectomized control group that was given a normal saline; or (iii) an ovariectomized + estrogen (100 µg/kg/day) group that was treated with conjugated equine estrogen. The right femur of all rats was fractured, and a Kirschner wire was inserted six weeks post-ovariectomy. Treatment with estrogen was given for another six weeks post-fracture. At the end of the study, blood samples were taken, and the right femur was harvested and subjected to biomechanical strength testing. RESULTS: The percentage change in the plasma TGF-β1 level before treatment was significantly lower in the ovariectomized control and estrogen groups when compared with the sham group (p<0.001). After six weeks of treatment, the percentage change in the plasma TGF-β1 level in the estrogen group was significantly higher compared with the level in the ovariectomized control group (p = 0.001). The mean ultimate force was significantly increased in the ovariectomized rats treated with estrogen when compared with the ovariectomized control group (p = 0.02). CONCLUSION: These data suggest that treatment with conjugated equine estrogen enhanced the strength of the healed bone in estrogen-deficient rats by most likely inducing the expression of TGF-β1.

The Effects of Cosmos caudatus on Structural Bone Histomorphometry in Ovariectomized Rats

Osteoporosis is considered a serious debilitating disease. Cosmos caudatus (ulam raja), a plant containing antioxidant compounds and minerals, may be used to treat and prevent osteoporosis. This study determines the effectiveness of C. caudatus as bone protective agent in postmenopausal osteoporosis rat model. Thirty-two female rats, aged 3 months old, were divided into 4 groups. Group one was sham operated (sham) while group two was ovariectomized. These two groups were given ionized water by forced feeding. Groups three and four were ovariectomized and given calcium 1% ad libitum and force-fed with C. caudatus at the dose of 500 mg/kg, respectively. Treatments were given six days per week for a period of eight weeks. Body weight was monitored every week and structural bone histomorphometry analyses of the femur bones were performed. Ovariectomy decreased trabecular bone volume (BV/TV), decreased trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Both calcium 1% and 500 mg/kg C. caudatus reversed the above structural bone histomorphometric parameters to normal level. C. caudatus shows better effect compared to calcium 1% on trabecular number (Tb.N) and trabecular separation (Tb.Sp). Therefore, Cosmos caudatus 500 mg/kg has the potential to act as the therapeutic agent to restore bone damage in postmenopausal women.

The effects of alpha-tocopherol supplementation on fracture healing in a postmenopausal osteoporotic rat model

OBJECTIVE: Osteoporosis increases the risk of bone fractures and may impair fracture healing. The aim of this study was to investigate whether alpha-tocopherol can improve the late-phase fracture healing of osteoporotic bones in ovariectomized rats. METHOD: In total, 24 female Sprague-Dawley rats were divided into three groups. The first group was sham-operated, and the other two groups were ovariectomized. After two months, the right femora of the rats were fractured under anesthesia and internally repaired with K-wires. The sham-operated and ovariectomized control rat groups were administered olive oil (a vehicle), whereas 60 mg/kg of alpha-tocopherol was administered via oral gavage to the alpha-tocopherol group for six days per week over the course of 8 weeks. The rats were sacrificed, and the femora were dissected out. Computed tomography scans and X-rays were performed to assess fracture healing and callus staging, followed by the assessment of callus strengths through the biomechanical testing of the bones. RESULTS: Significantly higher callus volume and callus staging were observed in the ovariectomized control group compared with the sham-operated and alpha-tocopherol groups. The ovariectomized control group also had significantly lower fracture healing scores than the sham-operated group. There were no differences between the alpha-tocopherol and sham-operated groups with respect to the above parameters. The healed femora of the ovariectomized control group demonstrated significantly lower load and strain parameters than the healed femora of the sham-operated group. Alpha-tocopherol supplementation was not able to restore these biomechanical properties. CONCLUSION: Alpha-tocopherol supplementation appeared to promote bone fracture healing in osteoporotic rats but failed to restore the strength of the fractured bone.

Vitamin E As a Potential Interventional Treatment for Metabolic Syndrome: Evidence from Animal and Human Studies

A constellation of medical conditions inclusive of central obesity, hyperglycemia, hypertension, and dyslipidemia is known as metabolic syndrome (MetS). The safest option in curtailing the progression of MetS is through maintaining a healthy lifestyle, which by itself, is a long-term commitment entailing much determination. A combination of pharmacological and non-pharmacological approach, as well as lifestyle modification is a more holistic alternative in the management of MetS. Vitamin E has been revealed to possess anti-oxidative, anti-inflammatory, anti-obesity, anti-hyperglycemic, anti-hypertensive and anti-hypercholesterolemic properties. The pathways regulated by vitamin E are critical in the development of MetS and its components. Therefore, we postulate that vitamin E may exert some health benefits on MetS patients. This review intends to summarize the evidence in animal and human studies on the effects of vitamin E and articulate the contrasting potential of tocopherol (TF) and tocotrienol (T3) in preventing the medical conditions associated with MetS. As a conclusion, this review suggests that vitamin E may be a promising agent for attenuating MetS.

Effects of metabolic syndrome on bone mineral density, histomorphometry and remodelling markers in male rats

This study aimed to evaluate the effects of metabolic syndrome (MetS) induced by high-carbohydrate high-fat (HCHF) diet on bone mineral density (BMD), histomorphometry and remodelling markers in male rats. Twelve male Wistar rats aged 12 weeks old were randomized into two groups. The normal group was given standard rat chow while the HCHF group was given HCHF diet to induce MetS. Abdominal circumference, blood glucose, blood pressure, and lipid profile were measured for the confirmation of MetS. Bone mineral density, histomorphometry and remodelling markers were evaluated for the confirmation of bone loss. The HCHF diet caused central obesity, hyperglycaemia, hypertension, and dyslipidaemia in male rats. No significant difference was observed in whole body bone mineral content and BMD between the normal and HCHF rats (p>0.05). For bone histomorphometric parameters, HCHF diet-fed animals had significantly lower osteoblast surface, osteoid surface, osteoid volume, and significantly higher eroded surface; resulting in a reduction in trabecular bone volume (p<0.05). Feeding on HCHF diet caused a significantly higher CTX-1 level (p<0.05), but did not cause any significant change in osteocalcin level compared to normal rats (p>0.05). In conclusion, HCHF diet-induced MetS causes imbalance in bone remodelling, leading to the deterioration of trabecular bone structure.

The Effects of a Modified High-carbohydrate High-fat Diet on Metabolic Syndrome Parameters in Male Rats

Metabolic syndrome is a cluster of metabolic abnormalities including central obesity, hyperglycemia, hypertension, and dyslipidemia. A previous study has established that high-carbohydrate high-fat diet (HCHF) can induce MetS in rats. In this study, we modified components of the diet so that it resembled the diet of Southeast Asians. This study aimed to determine the effects of this modified HCHF diet on metabolic parameters in rats. Male Wistar rats (n=14) were randomised into two groups. The normal group was given standard rat chow. The MetS group was given the HCHF diet, comprises of fructose, sweetened condensed milk, ghee, Hubble Mendel and Wakeman salt mixture, and powdered rat food. The diet regimen was assigned for a period of 16 weeks. Metabolic syndrome parameters (abdominal circumference, blood glucose, blood pressure, and lipid profile) were measured at week 0, 8, 12, and 16 of the study. The measurement of whole body composition (fat mass, lean mass, and percentage of fat) was performed using dual-energy X-ray absorptiometry at week 0, 8, and 16. Our results indicated that the components of MetS were partially developed after 8 weeks of HCHF diet. Systolic blood pressure, triglyceride, low density lipoprotein cholesterol, fat content, and percentage of fat was significantly higher in the HCHF group compared to normal group (p<0.05). After 12 weeks of HCHF diet, the rats showed significant increases in abdominal circumference, blood pressure, glucose intolerance, and dyslipidemia compared to normal control (p<0.05). In conclusion, MetS is successfully established in male rats induced by the modified HCHF diet after 12 weeks.