Bone-turnover marker (BTM) measurements in the blood or urine reflect the bone-remodeling rate and may be useful for studying and clinically managing metabolic bone diseases.Substantial evidence supporting the diagnostic use of BTMs has accumulated in recent years, together with the publication of several guidelines. Most clinical trials and observational and reference-interval studies have been performed in the Northern Hemisphere and have mainly involved Caucasian populations. This review focuses on the available data for populations from the Asia-Pacific region and offers guidance for using BTMs as diagnostic biomarkers in these populations. The procollagen I N-terminal propeptide and β-isomerized C-terminal telopeptide of type-I collagen (measured in plasma) are reference BTMs used for investigating osteoporosis in clinical settings. Premenopausal reference intervals (established for use with Asia-Pacific populations) and reference change values and treatment targets (used to monitor osteoporosis treatment) help guide the management of osteoporosis. Measuring BTMs that are not affected by renal failure, such as the bone-specific isoenzyme alkaline phosphatase and tartrate-resistant acid phosphatase 5b, may be advantageous for patients with advanced chronic kidney disease. Further studies of the use of BTMs in individuals with metabolic bone disease, coupled with the harmonization of commercial assays to provide equivalent results, will further enhance their clinical applications.

Dyslipidaemia is a recognised conventional risk factor for cardiovascular disease (CVD). However, even when traditional lipid parameters are normal, CVD risk can exist. Small dense lowdensity lipoprotein cholesterol (sdLDL) has appeared as a significant risk marker for CVD. This study aimed to determine the prevalence and associated factors of atherogenic lipoprotein Pattern B in the Malaysian population. Materials and Methods: This cross-sectional study included 150 subjects aged 30 years and above who attended a health screening in a Malaysian tertiary institution. Sociodemographics, clinical characteristics and laboratory parameters (lipids, glucose, and sdLDL) were obtained. Lipoprotein subfraction was analysed using the polyacrylamide gel electrophoresis method. Results: Malays and females made up the majority of subjects and the median age was 37 years. Normolipidaemic Pattern B was significantly higher in women (p=0.008). Significant independent predictors of Pattern B were gender (p=0.02), race (p=0.01), body mass index (BMI) [p=0.02] and lipid status (p=0.01). Triglyceride was the only independent predictor of sdLDL (p=0.001). Conclusion: The prevalence of Pattern B of 33% in this study was comparatively high, of which 6.7% were normolipidaemic. Chinese males with dyslipidaemia and increased BMI independently predicted Pattern B. Differences in triglyceride levels alone among these ethnic groups do not fully explain the differences in the prevalence of Pattern B although it was the only lipid parameter to independently predict sdLDL. Individuals with atherogenic normolipidaemia are at greater risk for a CVD event as they are not included in the protective measures of primary CVD prevention.

Interpretation of thyroid function test (TFT) is often straightforward but in certain scenarios, discordance between the clinical impression and the laboratory results exists. A 50-year-old woman with a ten years history of hypothyroidism on levothyroxine presented with a recent notable change in TFT [elevated free thyroxine (FT4) and thyroid-stimulating hormone (TSH)], in an otherwise clinically euthyroid and previously stable TFT, leading to levothyroxine being withheld. This case report highlights the possibility of assay interference as a cause of discordant TFT. It also draws the importance of close collaboration between clinicians and the laboratory to avoid unnecessary investigations and inappropriate management of such a case.

Introduction: Total calcium concentration is widely used to assess body calcium status although limited by many confounding factors. Thus, this study aimed to derive and internally validate an albumin-adjusted calcium equation for a selected Malaysian population. Method: This cross-sectional study involved 1011 adults at an emergency department of a tertiary hospital. Patients who had total calcium, ionised calcium and albumin measurements taken simultaneously were included. Derivation of the albumin-adjusted calcium equation was based on the adjustment equation obtained from the Association for Clinical Biochemistry and Laboratory Medicine 2015 position paper. Additionally, the equation was internally validated and compared with ionised calcium (gold standard) and the conventional Payne’s equation. Results: The newly derived equation = total calcium + 0.017 (41.35 – albumin). Internal validation exhibited the amount of shrinkage of 0.049. It tends to overestimate the adjusted calcium by a mean difference of 0.029 mmol/L compared to Payne’s equation. The comparison between Payne’s equation and the new equation with ionised calcium reclassified 402 and 486 patients, respectively into different calcium status. When both equations were compared, calcium status classification significantly differed in all and hypoalbuminaemic subjects by 90 and 16 patients, respectively. Conclusion: Locally derived albumin-adjusted calcium equation differed statistically in calcium status classification when compared to the Payne’s equation. However, to confirm this significance, the result must be compared to ionised calcium under strict, controlled preanalytical conditions. In terms of clinical significance, there was no difference in classification of calcium status between Payne’s and the new equation at medical decision limits.

Introduction: Prevention of osteoporotic fracture requires identification of individuals at high risk. Bone mineral density(BMD) is commonly used to estimate fracture probability despite inadequate predictive discrimination ability. Sphingosine-1-phosphate(S1P), a new marker of bone metabolism and bone turnover markers(BTM) such as procollagen-type-1 amino-terminal propeptide(P1NP) and C-terminal telopeptide of type I collagen(CTX) may complement current assessment. The study determined P1NP, CTX and S1P levels and their correlation with BMD, 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone(PTH) in selected subjects. Method: A cross-sectional study involving Malaysian Chinese men and women aged 50-90 years old from Puchong and Kajang, Selangor. Each subject had BMD determined by dual-energy x-ray absorptiometry and blood samples taken for 25(OH)D, PTH, P1NP, CTX and S1P. Results: A total of 131 subjects [45(34.4%) males and 86(65.6%) post-menopausal women] with median age of 65(IQR=17) were recruited. P1NP and CTX were significantly higher in post-menopausal women (P1NP=61.71 ng/ml, CTX=0.489 ng/ml) compared to men (P1NP=46.94 ng/ml, CTX=0.381 ng/ml). P1NP and CTX differed significantly according to BMD categories with values highest in osteoporosis. S1P between men (2.12±0.75 µmol/L) and post-menopausal women (1.96±0.68 µmol/L) did not differ significantly and did not differ according to BMD categories. S1P did not correlate with BMD, P1NP, CTX and 25(OH)D. P1NP and CTX negatively correlated with BMD at all measured sites but not 25(OH)D. Conclusion: CTX and P1NP, but not S1P negatively correlated with BMD. CTX and P1NP were highest in those with osteoporosis. In this group of Malaysian Chinese subjects, CTX and P1NP rather than S1P reflects bone health.

Congenital central hypothyroidism (CCH) is a rare disorder that results from deficient biosynthesis of thyroid hormone due to defective thyroid gland stimulation by thyroid stimulating hormone (TSH). Diagnosis is typically established biochemically by low free thyroxine (fT4) and inappropriately low or normal TSH levels after excluding all other causes of discordant thyroid function test (TFT). Here, we report a case of a baby girl who presented with prolonged jaundice at day 15 of life with normal cord blood TSH performed as routine screening for congenital hypothyroidism. Serial TFT revealed declining serum fT4 with normal TSH consistent with CCH. Her jaundice resolved prior to levothyroxine replacement. CCH is commonly missed on cord blood TSH-based newborn screening leading to a delay in diagnosis, potentially resulting in neurodevelopmental delay. Hence, although CCH has a lower incidence than congenital primary hypothyroidism, a high index of suspicion is essential for timely diagnosis.

Objectives: To determine the prevalence of osteopenia (OPe) and osteoporosis (OP) in an urban adult population in Malaysia, and to compare the change in the prevalence when using a Caucasian compared to an Asian reference range. Methods: A cross-sectional random sample of the population aged between 45 and 90 years from the state of Selangor, Malaysia, was invited to attend a bone health check-up. Participants with diseases known to affect bone metabolism or who were on treatment for OP were excluded. Bone mineral density was measured using dual energy X-ray absorptiometry. Based on the World Health Organization definitions, the prevalence of OPe and OP was calculated using the Asian and Caucasian T-scores. Results: A total of 342 subjects (222 females, 120 males), with a mean age of 59.68 (standard deviation: 8.89) years, who fulfilled the study criteria were assessed. Based on the Asian reference range, there were 140 (40.9%) subjects with OPe and 48 (14.0%) with OP. On applying the Caucasian reference range, there were 152 (44.4%) subjects with OPe and 79 (23.1%) with OP, with significant increases in males, females, and Chinese ethnic groups. Overall, 75 (21.9%) of subjects had a change in their diagnostic status. T-scores were consistently lower when the Caucasian reference range was used. Conclusions In a healthy urban Malaysian population, the prevalence of OP is 14.0% and OPe is 40.9%. Application of a Caucasian reference range significantly increased the number of subjects with OP and may potentially lead to over-treatment.

Objectives: To determine the prevalence of osteopenia (OPe) and osteoporosis (OP) in an urban adult population in Malaysia, and to compare the change in the prevalence when using a Caucasian compared to an Asian reference range. Methods: A cross-sectional random sample of the population aged between 45 and 90 years from the state of Selangor, Malaysia, was invited to attend a bone health check-up. Participants with diseases known to affect bone metabolism or who were on treatment for OP were excluded. Bone mineral density was measured using dual energy X-ray absorptiometry. Based on the World Health Organization definitions, the prevalence of OPe and OP was calculated using the Asian and Caucasian T-scores. Results: A total of 342 subjects (222 females, 120 males), with a mean age of 59.68 (standard deviation: 8.89) years, who fulfilled the study criteria were assessed. Based on the Asian reference range, there were 140 (40.9%) subjects with OPe and 48 (14.0%) with OP. On applying the Caucasian reference range, there were 152 (44.4%) subjects with OPe and 79 (23.1%) with OP, with significant increases in males, females, and Chinese ethnic groups. Overall, 75 (21.9%) of subjects had a change in their diagnostic status. T-scores were consistently lower when the Caucasian reference range was used. Conclusions In a healthy urban Malaysian population, the prevalence of OP is 14.0% and OPe is 40.9%. Application of a Caucasian reference range significantly increased the number of subjects with OP and may potentially lead to over-treatment.

Introduction: Low 25-hydroxyvitamin D [25(OH)D] levels have not been consistently associated with bone mineral density (BMD). It has been suggested that calculation of the free/bioavailable 25(OH)D may correlate better with BMD. We examined this hypothesis in a cohort of Malaysian women. Materials and Methods: A cross-sectional study of 77 patients with rheumatoid arthritis (RA) and 29 controls was performed. Serum 25(OH)D was measured using the Roche Cobas E170 immunoassay. Serum vitamin D binding protein (VDBP) was measured using a monoclonal enzymelinked immunosorbent assay (ELISA). Free/bioavailable 25(OH)D were calculated using both the modified Vermuelen and Bikle formulae. Results: Since there were no significant differences between RA patients and controls for VDBP and 25(OH)D, the dataset was analysed as a whole. Calculated free 25(OH)D by Vermeulen was strongly correlated with Bikle (r = 1.00, p < 0.001). A significant positive correlation was noted between measured total 25(OH)D with free/bioavailable 25(OH) D (r = 0.607, r = 0.637, respectively, p < 0.001). Median free/bioavailable 25(OH)D values were significantly higher in Chinese compared with Malays and Indians, consistent with their median total 25(OH)D. Similar to total 25(OH)D, the free/bioavailable 25(OH)D did not correlate with BMD. Conclusion: In this first study of a multiethnic female Malaysian population, free/bioavailable 25(OH)D were found to reflect total 25(OH)D, and was not superior to total 25(OH)D in its correlation with BMD. Should they need to be calculated, the Bikle formula is easier to use but only calculates free 25(OH)D. The Vermuelen formula calculates both free/bioavailable 25(OH)D but is more complex to use.
bone mineral density

Introduction: Statins have several pleiotropic effects including its primary effect of lipid lowering that is important to prevent cardiovascular disease (CVD). Subjects often have heterogeneous responses to statin. This study aims to determine the biochemical effects of statins on lipid parameters among newly diagnosed dyslipidaemia subjects. Methods: This was a prospective observational study involving 118 newly diagnosed adults with dyslipidaemia from three government health clinics in Selangor, Malaysia. Biochemical analyses including fasting lipid profile [triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C)] and apolipoproteins (apoA1, apoB) were taken at baseline and follow-up after a month on statin. Results: Majority of subjects (61.9%) were prescribed with lovastatin, with the rest on simvastatin. At baseline, the median values for all lipid profile parameters (TC, LDL-C, HDL-C) and non-conventional lipid parameters (LDL-C:HDL-C ratio, non-HDL-C, TC:HDL-C ratio, apoB:apoA1 ratio) were deranged except for TG and apoA1. On follow up, all parameters showed median values within the reference range except for HDL-C, non-HDL-C and TC:HDL-C ratio. There was significant difference in the effect of statins on lipid parameters including predictors of cardiovascular risk, simvastatin having better effects. Conclusions: Different statinshave varying effects on lipid parameters. Simvastatin showed significantly better effects compared to lovastatin. Non-HDL value should be included in the standard lipid profile report given its ease of use and implementation as it’s both a marker of coronary artery disease (CAD) risk stratification as well as an established determinant of goal attainment during therapy.