Different reference ranges affect the prevalence of osteoporosis and osteopenia in an urban adult Malaysian population

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.

Prolonged Neonatal Jaundice with Deranged Thyroid Function Test

@#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.

Bone Turnover Markers and Sphingosine-1-phosphate levels among the Chinese Community in Selangor, Malaysia and its Correlation with Bone Density

@#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.

Derivation and Internal Validation of an Equation for Albumin-adjusted Calcium at a Tertiary Hospital in Selangor, Malaysia

@#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.

Different reference ranges affect the prevalence of osteoporosis and osteopenia in an urban adult Malaysian population

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.

Misleading Free Thyroxine (FT4): A Case Report

@#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.

Biochemical Effects of Statins on Lipid Parameters among Newly Diagnosed Dyslipidaemia Subjects in Primary Care

@#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.

Calculation of free and bioavailable vitamin D and its association with bone mineral density in Malaysian women with rheumatoid arthritis

@#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.

Light chain multiple myeloma: an evaluation of its biochemical investigations

Multiple myeloma is a type of plasma cell dyscrasia, characterised by presence of paraprotein ormonoclonal (M)-protein in serum or urine. The M-protein may consist of an intact immunoglobulin,the heavy chain only or the light chain only. The latter, designated as light chain multiplemyeloma (LCMM) makes up almost 20% of myelomas. Clinical manifestation is often heraldedby hypercalcaemia, renal impairment, normocytic normochromic anaemia and bone lesions,reflecting end-organ damage, collectively known as the acronym CRAB. In particular, free lightchain nephrotoxicity accounts for the high prevalence of renal impairment seen in LCMM. Thiscase illustrates a typical presentation of LCMM with focal discussion on its initial and diagnostic,as well as prognostic biochemical investigations.

Determination of the 99th percentile upper reference limit for high-sensitivity cardiac troponin I in Malaysian population

Introduction of high-sensitivity cardiac troponin I (hscTn I) assays for routine clinical use in Malaysia requires determination of the 99th percentile upper reference limit (URL) for each assay to suit local context. Hence, this study aimed to determine the 99th percentile URL for hscTn I in the Malaysian population. A total of 250 (120 males and 130 females) healthy Malaysian blood donors aged 18 to 60 years old were recruited. Blood samples for hscTn I were measured using Abbott Diagnostics hscTn I assay on Architect i2000sr analyser. The 99th percentile was calculated using a non-parametric method and gender specific results were compared. The 99th percentile URL for hscTn I for the overall population was 23.7 ng/L, with gender specific values being 29.9 ng/L and 18.6 ng/L for male and female, respectively. Females had significantly lower hscTn I compared to males. This study confirms the use of gender specific 99th percentile URL for hscTn I for clinical use in a multi-ethnic Malaysian population.

A Brief Review on Free Light Chain Assays: From Conventional to Current

Free light chains (FLCs) are tumour markers of monoclonal gammopathies. Detection of urinary FLC or also known as Bence-Jones protein through urinary protein and its immunofixation electrophoreses (UPE and uIFE, respectively) have been considered the gold standard for its biochemical diagnosis. This is mainly due to their superior detection limits compared to their counterpart investigations in serum. However, urinalysis is limited in many ways. The emergence of serum FLC assay with markedly improved detection limit circumvents many of these problems and has gained much importance in biochemical investigations of monoclonal gammopathies. Nevertheless, they are not without limitations. This review discusses the advantages and limitations of serum and urinary FLC assays.

Trends in post osteoporotic hip fracture care from 2010 to 2014 in a private hospital in Malaysia

OBJECTIVE: Following an osteoporotic fracture, pharmacological treatment is recommended to increase bone mineral density and prevent future fractures. However, the rate of starting treatment after an osteoporotic hip fracture remains low. The objective of this study was to survey the treatment rate following a low-trauma hip fracture at a tertiary private hospital in Malaysia over a period of 5 years. METHODS: The computerised hospital discharge records were searched using the terms “hip,”“femur,”“femoral,”“trochanteric,”“fracture,” or “total hip replacement” for all patients over the age of 50, admitted between 2010 and 2014. The medical charts were obtained and manually searched for demographic data and treatment information. Hip operations done for non–low-trauma-related fracture and arthritis were excluded. RESULTS: Three hundred seventy patients over the age of 50 years were admitted with a hip fracture, of which 258 (69.7%) were low trauma, presumed osteoporotic, hip fractures. The median age was 79.0 years (interquartile range [IQR], 12.0). Following a hip fracture, 36.8% (95 of 258) of the patients received treatment, but out of these, 24.2% (23 of 95) were on calcium/vitamin D only. The median duration of treatment was 1 month (IQR, 2.5). In 2010, 56.7% of the patients received treatment, significantly more than subsequent years 2011–2014, where approximately only 30% received treatment. CONCLUSIONS: Following a low-trauma hip fracture, approximately 72% of patients were not started on active antiosteoporosis therapy. Of those who were, the median duration of treatment was 1 month. This represents a missed opportunity for the prevention of future fractures.

Relationship Between Dyslipidaemia And Glycaemic Status In Patients With Type 2 Diabetes Mellitus

The risk of coronary heart disease (CHD) is dramatically increased in diabetic patients due to their atherogenic lipid profile. The severity of CHD in diabetic patients has been found to be directly associated with glycated haemoglobin (HbA1c). According to the Malaysian Clinical Practice Guidelines on diabetes mellitus (DM), HbA1c level less than 6.5% reduces the risk of microvascular and macrovascular complications. Hence, this study aimed to determine the relationship between dyslipidaemia and glycaemic status in patients with type 2 DM (T2DM) patients in Hospital Putrajaya, a tertiary endocrine centre in Malaysia. This was a cross sectional, retrospective study of 214 T2DM patients with dyslipidaemia who had visited the endocrine clinic between January 2009 and December 2012. Significant correlations were found between fasting blood glucose (FBG) and HbA1c with total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL), non-high density lipoprotein cholesterol (non-HDL), LDL/HDL ratio and TC/HDL ratio; greater correlation being with HbA1c than FBG. In patients with HbA1c ≥ 6.5%, TC, TG, non-HDL and TC/HDL ratio were significantly higher than in patients with HbA1c < 6.5%. Non-HDL, LDL/HDL ratio, TC/HDL ratio and HbA1c were significantly lower in patients on statin treatment than nontreated patients (p<0.05). This significant association between glycaemic status and dyslipidaemia emphasises the additional possible use of HbA1c as a biomarker for dyslipidaemia as well as a potential indirect predictor of cardiovascular disease (CVD) risk in T2DM patients.

Practice Of Self-Monitoring Blood Glucose Among Insulin-treated Diabetic Patients In Hospital Serdang

Background: Diabetes Mellitus (DM), characterised by chronic hyperglycaemia, exposes patients to acute and chronic complications, such as hypoglycaemia and vascular complications, respectively. The latter is associated with the degree of glycaemic control. Glycated haemoglobin (HbA1c) indicates long-term glycaemic control of the preceding 2-3 months. The practice of self-monitoring blood glucose (SMBG) is essential for insulin-treated diabetic patients to achieve optimum glycaemic control and prevent hypoglycaemia. Aim: The study aimed to determine the SMBG practice and frequency and its association with HbA1c and factors in insulin-treated diabetic patients. Methods: This was a cross-sectional study of insulin-treated diabetic patients attending follow-up at the diabetic clinic of Hospital Serdang from April 2015 to August 2015. Consented eligible patients completed validated selfadministered questionnaires. Patients’ HbA1c results were obtained from the hospital information system. Results: Ninetyone of 137 (66%) patients practiced SMBG and 46 (34%) did not. Although 82% had seen diabetic nurses, 54% of patients did not alter their treatment accordingly. Neither the practice nor the frequency of SMBG was significantly associated with differences in HbA1c levels (p=0.334 and p=0.116 respectively). Ethnicity and household income significantly affected SMBG practice. The presence and frequency of hypoglycaemia significantly increased the likelihood of SMBG practice (p<0.001) and frequency (p<0.001). Conclusions: The prevalence of SMBG practice in diabetic patients on insulin was 66%. However, SMBG was not followed by proper treatment alteration in 54% of patients. There was no association between SMBG practice and frequency with good glycaemic control. Hypoglycaemia significantly affected the practice and frequency of SMBG.

Awareness of Glycosylated Haemoglobin (HbA1c) Among Type 2 Diabetes Mellitus Patients in Hospital Putrajaya

The glycosylated haemoglobin (HbA1c) test is the most widely accepted laboratory test for evaluating long term glycaemic control. Patient’s understanding of HbA1c can lead to better glycaemic control. This study is aimed to determine the awareness and level of understanding of HbA1c among type 2 DM patients and its association with glycaemic control. A cross-sectional descriptive study among Type 2 DM patients undergoing routine follow up in an endocrine clinic of a tertiary centre in Malaysia. Patients were invited to answer a validated questionnaire which assessed their awareness and understanding of HbA1c. Their last HbA1c results were retrieved from the laboratory information system. A total of 92 participants were recruited. Fifty-six (60.9%) were aware of the term HbA1c. Fifty percent were categorised as having good HbA1c understanding, with age, monthly income and level of education being the factors associated with understanding. No significant association was noted between HbA1c understanding and glycaemic control, although more patients with good HbA1c understanding had achieved the target glycaemic control compared to those with poor understanding. The level of HbA1c awareness and understanding was acceptable. Factors associated with understanding were age, income and level of education. Continuing efforts however, must be made to improve patients understanding of their disease and clinical disease biomarkers.

Prevalence of Dyslipidaemia in Type 2 Diabetes Mellitus Patients and Its Association to Diabetic Retinopathy in a Malaysian Tertiary Hospital

Background: Diabetic retinopathy (DR) is a microvascular complication of diabetes, which is a cause of visual impairment and blindness. Its development and progression have been linked to dyslipidaemia, although the link remains inconclusive. Aim: This study aimed to determine the prevalence of dyslipidaemia among type 2 diabetic patients with DR in a tertiary setting and to determine the association between dyslipidaemia and DR severity. Materials and methods: This was a cross sectional study using retrospective data of type 2 diabetic patients attending the opthalmology clinic of a tertiary centre from January 2007 to June 2014. Results of their fasting lipid profile and clinical data were retrieved from the hospital information system. Results: A total of 178 patient’s data were collected. 120 (n=67.4%) patients had non-proliferative diabetic retinopathy (NDPR) with moderate NPDR being the most prevalent. Dyslipidaemia was noted in 151 (84.8%) of the patients. Patients had a combination of more than one abnormality in the lipid profile with increased LDL-cholesterol being the main abnormality. Dyslipidaemia was however, not significantly associated with DR severity. Conclusion: Dyslipidaemia was highly prevalent in DR patients. The dyslipidaemia was however not associated with severity of DR.