Fairus Ahmad

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.

Testosterone is associated with age-related changes in bone health status, muscle strength and body composition in men

Objective: Variations in testosterone levels are associated with several outcomes of aging. The present study aimed to examine the relationship between age-related decline of testosterone levels and changes in bone health status, handgrip strength, body fat percentage and fat-free mass. Materials and methods: A total of 335 Malaysian Chinese and Malay men aged 40 years and above were recruited for this study. Their body compositions, calcaneal speed of sound and handgrip strength were measured and their blood was collected. Linear regression analysis was done to examine the relationship among age, testosterone levels and outcomes of aging. Results: The results indicated significant changes in all testosterone measurements, sex hormone binding globulin level, calcaneal speed of sound, handgrip strength, body fat percentage and fat-free mass with age (p < 0.05). Age-dependent decline in bioavailable and free testosterone levels were significantly associated with reduction in calcaneal speed of sound, fat-free mass and handgrip strength (p < 0.05). Age-dependent decline in the total testosterone level was significantly associated with an increase in body fat percentage among the elderly men (p < 0.05). Conclusion: Testosterone levels are associated with changes in outcome of aging such as bone health status, muscle strength and body composition, and the relationships are age-dependent.

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.

Sex hormones in Malay and Chinese men in Malaysia: are there age and race differences?

OBJECTIVES: Variations in the prevalence of sex-hormone-related diseases have been observed between Asian ethnic groups living in the same country; however, available data concerning their sex hormone levels are limited. The present study aimed to determine the influence of ethnicity and age on the sex hormone levels of Malay and Chinese men in Malaysia. METHODS: A total of 547 males of Malay and Chinese ethnicity residing in the Klang Valley Malaysia underwent a detailed screening, and their blood was collected for sex hormones analyses. RESULTS: Testosterone levels were normally distributed in the men (total, free and non-sex hormone-binding globulin (SHBG) bound fractions), and significant ethnic differences were observed (p<0.05); however, the effect size was small. In general, testosterone levels in males began to decline significantly after age 50. Significant ethnic differences in total, free and non-SHBG bound fraction estradiol levels were observed in the 20-29 and 50-59 age groups (p<0.05). The estradiol levels of Malay men decreased as they aged, but they increased for Chinese men starting at age 40. CONCLUSIONS: Small but significant differences in testosterone levels existed between Malay and Chinese males. Significant age and race differences existed in estradiol levels. These differences might contribute to the ethnic group differences in diseases related to sex hormones, which other studies have found in Malaysia.

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.

Osteoporosis is associated with metabolic syndrome induced by high-carbohydrate high-fat diet in a rat model

This study aimed to investigate the bone quality in rats induced with metabolic syndrome (MetS) using high-carbohydrate high-fat (HCHF) diet. Male Wistar rats (n = 14) were randomized into two groups. The normal group was given standard rat chow. The MetS group was given HCHF diet. Diet regimen was assigned for a period of 20 weeks. Metabolic syndrome parameters were measured monthly until MetS was established. Left tibiae were scanned using micro-computed tomography at week 0, 8, 12, 16, and 20 to analyze the trabecular and cortical bone structure. At the end of the study, rats were euthanized and their bones were harvested for analysis. Metabolic syndrome was established at week 12 in the HCHF rats. Significant deterioration of trabecular bone was observed at week 20 in the HCHF group (p < 0.05). The HCHF diet also decreased cortical and tissue area significantly (p < 0.05), but did not affect cortical thickness and bone calcium content (p > 0.05). Femur length and width in the HCHF group were significantly shorter than the normal group (p < 0.05). The biomechanical strength test showed that the femur of the HCHF rats could endure significantly lower force, but significantly higher displacement and strain compared to the normal rats (p < 0.05). In conclusion, HCHF diet-induced MetS can cause adverse effects on the bone.

Piper Sarmentosum: A New Hope for the Treatment of Osteoporosis

Osteoporosis is a major global health problem. Osteoporosis is characterized by the loss of bone mass and strength which leads to an increased risk of fracture. Glucocorticoid treatment is the leading cause of secondary osteoporosis. Glucocorticoid action in bone depends upon the expression of 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). The oestrogen deficient state causes osteoporosis due to enhancement of osteoclastogenesis by oxidative stress which leads to increased bone resorption. Piper sarmentosum (Daun Kaduk) is commonly used in the local cuisine of South East Asia. It is also traditionally used to treat many diseases such as inflammation, dermatitis and joint pain. Studies have revealed antioxidant properties through its flavonoids compound naringenin which acts as a superoxide scavenger that may help in the endogenous antioxidant defence system to protect bone against osteoporosis. Recent studies found that Ps extract has the ability to inhibit the expression and activity of 11β-HSD1 in adipose tissue and bone which restored bone structure and strength. It also accelerates fracture healing in the oestrogen deficient state through its antioxidant properties. The cost of conventional treatment is high and together with the adverse effects it leads to noncompliance. Treatment modalities with herbal medicine, less side effects and is cheaper need to be explored.This review focused on the therapeutic effect of Ps extract on fracture healing in ovariectomized rats and its protective effects against glucocorticoid induced osteoporotic rats.

Histomorphometric changes in the perirenal adipocytes of adrenalectomized rats treated with dexamethasone

INTRODUCTION: Prolonged steroid treatment administered to any patient can cause visceral obesity, which is associated with metabolic disease and Cushings syndrome. Glucocorticoids have a profound negative effect on adipose tissue mass, giving rise to obesity, which in turn is regulated by the 11β-hydroxysteroid dehydrogenase type 1 enzyme. Adrenalectomized rats treated with dexamethasone exhibited an increase in visceral fat deposition but not in body weight. OBJECTIVES: The main aim of this study was to determine the effect of dexamethasone on the histomorphometric characteristics of perirenal adipocytes of adrenalectomized, dexamethasone-treated rats (ADR+Dexa) and the association of dexamethasone treatment with the expression and activity of 11β-hydroxysteroid dehydrogenase type 1 (11β- hydroxysteroid dehydrogenase type 1). METHODS: A total of 20 male Sprague Dawley rats were divided into 3 groups: a baseline control group (n = 6), a sham-operated group (n = 7) and an adrenalectomized group (n = 7). The adrenalectomized group was given intramuscular dexamethasone (ADR+Dexa) 2 weeks post adrenalectomy, and the rats from the sham-operated group were administered intramuscular vehicle (olive oil). RESULTS: Treatment with 120 µg/kg intramuscular dexamethasone for 8 weeks resulted in a significant decrease in the diameter of the perirenal adipocytes (p<0.05) and a significant increase in the number of perirenal adipocytes (p<0.05). There was minimal weight gain but pronounced fat deposition in the dexamethasone-treated rats. These changes in the perirenal adipocytes were associated with high expression and dehydrogenase activity of 11β-hydroxysteroid dehydrogenase type 1. CONCLUSIONS: In conclusion, dexamethasone increased the deposition of perirenal fat by hyperplasia, which causes increases in the expression and dehydrogenase activity of 11β-hydroxysteroid dehydrogenase type 1 in adrenalectomized rats.

Insulin-like growth factor-1 is a mediator of age-related decline of bone health status in men

Abstract Objective: The role of insulin-like growth factor-1 (IGF-1) in bone health in men is debatable. This study aimed to determine whether IGF-1 is a mediator in age-related decline of bone health status measured by calcaneal speed of sound (SOS) in Malaysian men. Methods: The study recruited 279 Chinese and Malay men. Their demographic data, weight, height, calcaneal SOS were taken and fasting blood was collected for total testosterone, sex-hormone binding globulin and IGF-1 assays. The associations between the studied variables were assessed using multiple linear regression (MLR) analysis. Mediator analysis was performed using Sobel test. Results: There was a significant and parallel decrease of IGF-1 and SOS with age (p < 0.05). Serum IGF-1 was significantly and positively associated with SOS (p < 0.05) but after further adjustment for age, the significance was lost (p > 0.05). The strength of the association between age and SOS decreased after adjusting for IGF-1 level but it remained significant (p < 0.05). Sobel test revealed that IGF-1 was a significant partial mediator in the relationship between age and SOS (z = −4.3). Conclusion: Serum IGF-1 is a partial mediator in the age-related decline of bone health in men as determined by calcaneal ultrasound. A prospective study should be performed to validate this relationship.