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Musicians are always talking about ‘shape’ in reference to phrasing, but mostly I think they merely mean that something has shape rather than being ‘shapeless’—always a derogatory term. Shape in this sense means direction, a start and a finish with something pleasing in the middle. Seldom are the visual patterns of a draughtsman or an artist relevant to a musician. Nevertheless, only today I was doing an interview and trying to describe to the journalist a CD I recently recorded of music by Scriabin and Janáček. Strange bedfellows, it would seem, despite some parallels in their Slavic origins and their eccentric visions. But what makes them so different from each other (and therefore fascinating in juxtaposition) is actually related to shape. Scriabin is all seductive curves (across the phrases and up through the exotic harmonies), whereas Janáček is angular and fragmented, motives repeated and insisted on like an army of elbows. Perfumed ...

To cite this article: Zollner EW, Lombard C, Galal U, Hough S, Irusen E, Weinberg E. Hypothalamic–pituitary–adrenal axis suppression in asthmatic children on inhaled and nasal corticosteroids: is the early-morning serum adrenocorticotropic hormone (ACTH) a useful screening test? Pediatr Allergy Immunol 2011; 22: 614–620. Abstract Background: Hypothalamic–pituitary–adrenal axis suppression (HPAS) in asthmatic children treated with inhaled corticosteroids (ICS), with or without nasal steroids (NS), may be more common than previously thought. Only dynamic testing will identify children at risk of adrenal crisis. It is impractical to test all asthmatic children for HPAS with a gold standard adrenal function test, i.e. the metyrapone or insulin tolerance test. Objective: To determine which clinical or biochemical parameter is the most useful screening test for HPAS in asthmatic children. Methods: Twenty-six asthmatic children, 5–18 yr old, on ICS ± NS, not treated with oral or topical steroids in the preceding year were recruited. Height, weight, height velocity, weight velocity and a change in systolic blood pressure from the recumbent to the standing position (ΔSBP) were recorded. Early-morning urine for urinary free cortisol (UFC) and urinary cortisol metabolites (UCM) was collected. UFC was analysed by both a chemiluminescent assay and gas chromatography/mass spectrometry (GC-MS). Morning serum cortisol and adrenocorticotropic hormone (ACTH) levels were measured. The overnight metyrapone test was performed if the fasting morning serum cortisol was >83 nmol/l. HPAS was diagnosed if the ACTH failed to rise >100 pg/ml after metyrapone. Spearman correlation coefficients (r) were calculated between the post-metyrapone ACTH and each variable. A receiver-operating characteristics (ROC) curve was drawn for the most promising test, and the diagnostic performance was calculated. Results: All clinical and biochemical parameters investigated were weakly and non-significantly correlated with the post-metyrapone ACTH, except for the morning serum ACTH (r = 0.68; p

Glucocorticoid-induced osteoporosis (GCOP) is predominantly caused by inhibition of bone formation, resulting from a decrease in osteoblast numbers. Employing mouse (MBA-15.4) and human (MG-63) osteoblast cell lines, we previously found that the glucocorticoid (GC) dexamethasone (Dex) inhibits cellular proliferation as well as activation of the MAPK/ERK signaling pathway, essential for mitogenesis in these cells, and that both these effects could be reversed by the protein tyrosine phosphatase (PTP) inhibitor vanadate. In a rat model of GCOP, the GC-induced changes in bone formation, mass, and strength could be prevented by vanadate cotreatment, suggesting that the GC effects on bone were mediated by one or more PTPs. Employing phosphatase inhibitors, qRT-PCR, Western blotting, and overexpression/knockdown experiments, we concluded that MKP-1 was upregulated by Dex, that this correlated with the dephosphorylation of ERK, and that it largely mediated the in vitro effects of GCs on bone. To confirm the pivotal role of MKP-1 in vivo, we investigated the effects of the GC methylprednisolone on the quantitative bone histology of wild-type (WT) and MKP-1 homozygous knockout (MKP-1(-/-)) mice. In WT mice, static bone histology revealed that GC administration for 28 days decreased osteoid surfaces, volumes, and osteoblast numbers. Dynamic histology, following time-spaced tetracycline labeling, confirmed a significant GC-induced reduction in osteoblast appositional rate and bone formation rate. However, identical results were obtained in MKP-1 knockout mice, suggesting that in these animals upregulation of MKP-1 by GCs cannot be regarded as the sole mediator of the GC effects on bone.

As highlighted in earlier chapters, diabetes mellitus is associated with an increased risk for low-trauma fractures [1, 2]. In the case of Type 1 diabetes (T1DM) this is at least partially mediated through lower bone mineral density (BMD) as reflected by routine clinical measurements such as dual energy X-ray absorptiometry (DXA) [2]. The situation with Type 2 diabetes (T2DM) is clearly more complicated since BMD measurements are typically increased. In view of the differences in underlying pathophysiology and how this may mediate its effects on subsequent fractures, it is unlikely that a single approach for fracture risk assessment will be equally applicable to T1DM and T2DM. Given the preponderance of T2DM among older individuals, the segment of the population at highest risk for osteoporotic fractures, and the BMD-fracture paradox alluded to earlier, this chapter will emphasize considerations in T2DM.

The National Osteoporosis Foundation of South Africa (NOFSA) was established in 1993 to heighten awareness and increase knowledge on osteoporosis, to promote research in the field, and above all to improve the care of patients suffering from this common, serious disease. The Foundation has always aspired to ensure access, for all those suffering from osteoporosis, to modern diagnostic facilities and effective, safe medication to treat this disease.

Cassim et al are to be commended on their detailed and clear recommendations for the acute and longterm medical management of osteoporotic hip fractures, published in a recent issue of JEMDSA. 1 This publication, a position paper of the National Osteoporosis Foundation of South Africa (NOFSA) and the South African Geriatrics Society, comes at a most opportune time, as it coincides with the launch of the Capture the Fracture campaign of the International Osteoporosis Foundation (IOF) and the 2 Million 2 Many initiative of the American Society for Bone and Mineral Research (ASBMR). Both of these programmes aim to emphasise the fact that a mere one in every 10 patients with hip fractures is afforded proper prophylactic therapy to prevent subsequent fractures. 2 This is particularly unfortunate, given the fact that hip fractures carry high mortality (20-36%) and morbidity (less than 50% of patients with hip fractures are capable of leading an independent existence following a hip fracture), yet are very amenable to preventive therapy (a 30-50% reduction in fracture risk). 3

Genomic medicine is based on the knowledge that virtually every medical condition, disease susceptibility or response to treatment is caused, regulated or influenced by genes. Genetic testing may therefore add value across the disease spectrum, ranging from single-gene disorders with a Mendelian inheritance pattern to complex multi-factorial diseases. The critical factors for genomic risk prediction are to determine: (1) where the genomic footprint of a particular susceptibility or dysfunction resides within this continuum, and (2) to what extent the genetic determinants are modified by environmental exposures. Regarding the small subset of highly penetrant monogenic disorders, a positive family history and early disease onset are mostly sufficient to determine the appropriateness of genetic testing in the index case and to inform pre-symptomatic diagnosis in at-risk family members. In more prevalent polygenic non-communicable diseases (NCDs), the use of appropriate eligibility criteria is required to ensure a balance between benefit and risk. An additional screening step may therefore be necessary to identify individuals most likely to benefit from genetic testing. This need provided the stimulus for the development of a pathology-supported genetic testing (PSGT) service as a new model for the translational implementation of genomic medicine in clinical practice. PSGT is linked to the establishment of a research database proven to be an invaluable resource for the validation of novel and previously described gene-disease associations replicated in the South African population for a broad range of NCDs associated with increased cardio-metabolic risk. The clinical importance of inquiry concerning family history in determining eligibility for personalized genotyping was supported beyond its current limited role in diagnosing or screening for monogenic subtypes of NCDs. With the recent introduction of advanced microarray-based breast cancer subtyping, genetic testing has extended beyond the genome of the host to also include tumor gene expression profiling for chemotherapy selection. The decreasing cost of next generation sequencing over recent years, together with improvement of both laboratory and computational protocols, enables the mapping of rare genetic disorders and discovery of shared genetic risk factors as novel therapeutic targets across diagnostic boundaries. This article reviews the challenges, successes, increasing inter-disciplinary integration and evolving strategies for extending PSGT towards exome and whole genome sequencing (WGS) within a dynamic framework. Specific points of overlap are highlighted between the application of PSGT and exome or WGS, as the next logical step in genetically uncharacterized patients for whom a particular disease pattern and/or therapeutic failure are not adequately accounted for during the PSGT pre-screen. Discrepancies between different next generation sequencing platforms and low concordance among variant-calling pipelines caution against offering exome or WGS as a stand-alone diagnostic approach. The public reference human genome sequence (hg19) contains minor alleles at more than 1 million loci and variant calling using an advanced major allele reference genome sequence is crucial to ensure data integrity. Understanding that genomic risk prediction is not deterministic but rather probabilistic provides the opportunity for disease prevention and targeted treatment in a way that is unique to each individual patient.

Glucocorticoid (GC)-induced osteoporosis has been attributed to a GC-induced suppression of pre-osteoblast proliferation. Our previous work identified a critical role for mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in mediating the anti-proliferative effects of GCs in immortalized pre-osteoblasts, but we subsequently found that MKP-1 null mice were not protected against the pathological effects of GCs on bone. In order to reconcile this discrepancy, we have assessed the effects of GCs on proliferation, activation of the MAPK ERK1/2 and MKP-1 expression in primary adipose-derived stromal cells (ADSCs) and ADSC-derived pre-osteoblasts (ADSC-OBs). ADSCs were isolated by means of collagenase digestion from adipose tissue biopsies harvested from adult male Wistar rats. ADSC-OBs were prepared by treating ADSCs with osteoblast differentiation media for 7 days. The effects of increasing concentrations of the GC dexamethasone on basal and mitogen-stimulated cell proliferation were quantified by tritiated thymidine incorporation. ERK1/2 activity was measured by Western blotting, while MKP-1 expression was quantified on both RNA and protein levels, using semi-quantitative real-time PCR and Western blotting, respectively. GCs were strongly anti-proliferative in both naive ADSCs and ADSC-OBs, but had very little effect on mitogen-induced ERK1/2 activation and did not upregulate MKP-1 protein expression. These findings suggest that the anti-proliferative effects of GCs in primary ADSCs and ADSC-OBs in vitro do not require the inhibition of ERK1/2 activation by MKP-1, which is consistent with our in vivo findings in MKP-1 null mice.

Black women are generally regarded as being less prone to the development of osteoporosis. This study reports a similar prevalence of morphometric vertebral fractures in black (9.1 %) and white (5.0 %) South African women. Clinical risk factors and bone strength parameters contributed differently to fracture risk in the two ethnic cohorts. Vertebral fracture represents one of the most common osteoporotic fractures and is a significant cause of morbidity and mortality. Little is known regarding the prevalence of vertebral fractures on the African continent. We therefore prospectively examined the prevalence of vertebral fracture on radiographs of the thoraco-lumbar spine in otherwise healthy community-dwelling older black and white South African women. Radiographs of the spine (T4–L5) were obtained randomly in 189 women (47 % black), aged 40 years or older, for the analysis of vertebral fracture. Radiographs were evaluated by a single radiologist, blinded to clinical data, using Genant’s semi-quantitative method. Clinical risk factors for osteoporosis, risk factors for falls (fall history, quadriceps strength, lateral sway and reaction time), areal and volumetric bone mineral density of the spine and hip, calcaneal ultrasonography (QUS) and vertebral macro-geometry were assessed in the two ethnic groups and the association with prevalent vertebral fractures examined. Vertebral fracture prevalence in older South African black and white women was similar (9.1 % in black and 5.0 % in white women). In black women, lower body weight and lower areal and volumetric bone mineral density (BMD) at all sites could serve as markers of increased fracture risk. Older age, physical inactivity, lower muscle strength and lower femoral BMD were associated with vertebral fracture risk in whites. Our findings are noteworthy and the first attempt to compare vertebral fracture risk in women of different ethnicities on the African continent. A similar vertebral fracture risk between black and white women in South Africa must be considered at present to ensure appropriate evaluation in all subjects who present with clinical risk factors for osteoporosis, regardless of ethnicity.

Ethnic differences in bone mineral density (BMD) between healthy adult black and white South African women were studied. Higher BMD was only noted at the femoral sites in black women. Body weight significantly impacted these findings. A lower fracture risk at all skeletal sites cannot be assumed in black South African (SA) women.Bone mineral density (BMD) varies amongst women of different ethnicities. African-Americans have higher BMD at all skeletal sites compared with whites. On the African continent, bone density studies suggest site-specific ethnic differences in BMD. To examine the contribution of body weight and lifestyle characteristics to ethnic differences in BMD between adult black and white South African women, we assessed lumbar spine (SBMD), femoral neck (FNBMD) and total femoral BMD (FTBMD) by dual-energy X-ray absorptiometry (DXA) in 184 black and 143 white women aged between 23 and 82 years.BMDs were compared amongst pre- and postmenopausal blacks and whites before and after adjustment for covariates with significant univariate association with BMD. Volumetric bone mineral apparent density (BMAD) of the spine and femoral neck was also calculated to account for ethnic differences in bone size.Before adjustment, SBMD was lower (p 0.05), FTBMD similar and FNBMD (p 0.01) higher in premenopausal black women. Similar SBMD, but significantly higher BMD at the femoral sites (p 0.01), was noted in postmenopausal blacks compared with whites. Amongst anthropometric measures and lifestyle factors, only adjustment for weight significantly altered these observed ethnic differences in bone density. After adjustment for weight, SBMD remained lower in premenopausal blacks and became lower in young postmenopausal blacks. Weight adjustment eliminated all ethnic differences in proximal femoral BMD measurements, with the exception of FNBMD that remained higher in younger postmenopausal blacks. Before adjustment, calculated SBMAD was similar and FNBMAD consistently higher in blacks in all the menstrual groups. Adjustment for weight did not alter these findings.Most of the observed ethnic difference in BMD was explained by differences in body weight between black and white SA women. The higher femoral BMD in older blacks may explain, the lower hip fracture prevalence in black South African women. The lower SBMD in pre- and postmenopausal black women in this study suggests that factors other than BMD should be considered to explain a lower vertebral fracture prevalence in blacks, if a lower fracture prevalence does indeed exist.

Following the publication of an article by Mark Bolland and coworkers in the British Medical Journal of 29 July 2010, on the association between calcium supplementation for osteoporosis and an increased risk of myocardial infarction, much concern and confusion exist among patients and doctors alike as to the safety and efficacy of these agents.

The association between type 2 diabetes mellitus (T2DM), obesity, hypertension, dyslipidaemia, hyperuricaemia and coronary vascular disease (CVD) was recorded more than 70 years ago, and in 1977 Haller coined the term metabolic syndrome (MS) to describe this group of disorders.

No Abstract. Journal of Endocrinology, Metabolism and Diabetes of South Africa Vol. 10(2) 2005: 51-53

Objective To determine which parameter is the most useful screening test for hypothalamic–pituitary–adrenal suppression in asthmatic children. Design Cross-sectional study. Setting Paediatric allergy clinics in Cape Town, South Africa. Participants 143 asthmatic children of mostly mixed ancestry, aged 5–12 years. Outcome measures Primary outcome measures included Spearman correlation coefficients (r) calculated between the postmetyrapone (PMTP) serum adrenocorticotropic hormone (ACTH), 11-deoxycortisol (11DOC), 11DOC+ cortisol (C) and height, weight, height velocity, weight velocity, change in systolic blood pressure from supine to standing, early morning urinary free cortisol (UFC), morning C, ACTH and dehydroepiandrosterone sulfate (DHEAS). Secondary outcome measures were the receiver operating characteristics (ROC) curve and the diagnostic statistics for the most promising test. Results All screening variables were weakly correlated with the three PMTP outcomes. Only DHEAS and UFC (nmol/m 2 ) were statistically significant—DHEAS for PMTP ACTH and 11DOC (r=0.20, p=0.025 and r=0.21, p=0.017); UFC (nmol/m 2 ) for PMTP 11DOC and 11DOC+C (r=0.19, p=0.033 and r=0.20, p=0.022). The area under ROC curve for DHEAS in the 5-year to 9-year age group was 0.69 (95% CI 0.47 to 0.92). At DHEAS cut-off of 0.2 µmol/L: sensitivity=0.88 (CI 0.47 to 1.00), specificity=0.61 (CI 0.42 to 0.78), positive predictive value=0.37 (CI 0.16 to 0.62), negative predictive value=0.95 (CI 0.75 to 1.00), accuracy=0.67 (CI 0.50 to 0.81), positive likelihood ratio=2.26 (CI 1.35 to 3.78), negative likelihood ratio=0.20 (CI 0.03 to 1.30). Conclusions No parameter is useful as a universal screening test. DHEAS may be suitable to exclude HPAS before adrenarche. Further research is needed to confirm these findings and identify factors, for example, genetic that may predict or protect against HPAS.

Insulin resistance (IR) is thought to underlie the development of a number of clinically important disorders, including type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), hypertension, polycystic ovary syndrome (PCOS), and non-alcoholic fatty liver disease (NAFLD).

Background Despite changes in WHO guidelines, stavudine is still used extensively for treatment of pediatric HIV in the developing world. Lipoatrophy in sub-Saharan African children can be stigmatizing and have far-reaching consequences. The severity and extent of lipoatrophy in pre-pubertal children living in sub-Saharan Africa is unknown. Methods In this cross-sectional study, children who were 3-12 years old, on antiretroviral therapy and pre-pubertal were recruited from a Family HIV Clinic in South Africa. Lipoatrophy was identified and graded by consensus between two HIV pediatricians using a standardized grading scale. A professional dietician performed formal dietary assessment and anthropometric measurements of trunk and limb fat. Previous antiretroviral exposures were recorded. In a Dual-Energy X-ray Absorbtiometry (DXA) substudy body composition was determined in 42 participants. Results Among 100 recruits, the prevalence of visually obvious lipoatrophy was 36% (95% CI: 27%–45%). Anthropometry and DXA measurements corroborated the clinical diagnosis of lipoatrophy: Both confirmed significant, substantial extremity fat loss in children with visually obvious lipoatrophy, when adjusted for age and sex. Adjusted odds ratio for developing lipoatrophy was 1.9 (95% CI: 1.3 - 2.9) for each additional year of accumulated exposure to standard dose stavudine. Cumulative time on standard dose stavudine was significantly associated with reductions in biceps and triceps skin-fold thickness (p=0.008). Conclusions The prevalence of visually obvious lipoatrophy in pre-pubertal South African children on antiretroviral therapy is high. The amount of stavudine that children are exposed to needs review. Resources are needed to enable low-and-middle-income countries to provide suitable pediatric-formulated alternatives to stavudine-based pediatric regimens. The standard stavudine dose for children may need to be reduced. Diagnosis of lipoatrophy at an early stage is important to allow timeous antiretroviral switching to arrest progression and avoid stigmatization. Diagnosis using visual grading requires training and experience, and DXA and comprehensive anthropometry are not commonly available. A simple objective screening tool is needed to identify early lipoatrophy in resource-limited settings where specialized skills and equipment are not available.

BACKGROUND AND OBJECTIVE: Hypothalamic-pituitary-adrenal axis suppression (HPAS) when treating children with corticosteroids is thought to be rare. Our objective was to determine the prevalence of and predictive factors for various degrees of HPAS. METHODS: Clinical features of HPAS, doses, adherence, asthma score, and lung functions were recorded in 143 asthmatic children. The overnight metyrapone test was performed if morning cortisol was >83 nmol/L. Spearman correlations coefficients ( r ) were calculated between 3 postmetyrapone outcomes and each continuous variable. A multiple linear regression model of √postmetyrapone adrenocorticotropic hormone (ACTH) and a logistic regression model for HPAS were developed. RESULTS: Hypocortisolemia was seen in 6.1% (1.8–10.5), hypothalamic-pituitary suppression (HPS) in 22.2% (14.5–29.9), adrenal suppression in 32.3% (23.7–40.9), HPAS in 16.3% (9.3–23.3), and any hypothalamic-pituitary-adrenal axis dysfunction in 65.1% (56.5–72.9). Log daily nasal steroid (NS) dose/m2 was associated with HPAS in the logistic regression model (odds ratio = 3.7 [95% confidence interval: 1.1–13.6]). Daily inhaled corticosteroids (ICSs) + NS dose/m2 predicted HPAS in the univariate logistic regression model ( P = .038). Forced expiratory volume in 1 second/forced vital capacity

Background: Hypothalamic pituitary adrenal axis suppression (HPAS) when treating asthmatic children with inhaled corticosteroids (ICS) is thought to be rare. Objective: To determine the prevalence of HPAS in asthmatic children treated with ICS and nasal steroids (NS). Methods: Twenty-six asthmatic children were recruited. Clinical features of HPAS, height, weight, height and weight velocity, steroid dose, adherence, symptom control and lung functions were documented. Metyrapone test was performed if the serum cortisol was > 83 nmol/L ( > 3 µ g/dL). Results: No child had a serum cortisol < 83 nmol/L ( < 3 µ g/dL). Prevalence of HPAS was 35 (CI = 17 % – 56 % ). Daily NS dose/ m 2 and cumulative NS dose/m 2 were signifi cantly (p = 0.03) inversely correlated with the post-metyrapone ACTH (r = – 0.42 for both). Current ICS dose was not associated with the post-metyrapone ACTH (r = 0). There was a weak correlation with the daily ICS dose/m 2 (r = – 0.12) and cumulative ICS dose/m 2 (r = – 0.26). Conclusions: A third of asthmatic children on ICS and NS develop HPAS. Contributing factors are the use of NS, body size and cumulative dose of ICS.

Steroid-induced osteoporosis is a common side effect of long-term treatment with glucocorticoid (GC) drugs. GCs have multiple systemic effects that may influence bone metabolism but also directly affect osteoblasts by decreasing proliferation. This may be beneficial at low concentrations, enhancing differentiation. However, high-dose treatment produces a severe deficit in the proliferative osteoblastic compartment. We provide causal evidence that this effect of GC is mediated by induction of the dual-specificity MAPK phosphatase, MKP-1/DUSP1. Excessive MKP-1 production is both necessary and sufficient to account for the impaired osteoblastic response to mitogens. Overexpression of MKP-1 after either GC treatment or transfection ablates the mitogenic response in osteoblasts. Knockdown of MKP-1 using either immunodepletion of MKP-1 before in vitro dephosphorylation assay or short interference RNA transfection prevents inactivation of ERK by GCs. Neither c-jun N-terminal kinase nor p38 MAPK is activated by the mitogenic cocktail in 20% fetal calf serum, but their activation by a DNA-damaging agent (UV irradiation) was inhibited by either GC treatment or overexpression of MKP-1, indicating regulation of all three MAPKs by MKP-1 in osteoblasts. However, an inhibitor of the MAPK/ERK kinase-ERK pathway inhibited osteoblast proliferation whereas inhibitors of c-jun N-terminal kinase or p38 MAPK had no effect, suggesting that ERK is the MAPK that controls osteoblast proliferation. Regulation of ERK by MKP-1 provides a novel mechanism for control of osteoblast proliferation by GCs.

Osteoporosis is defined by the World Health Organization (WHO) as a systemic skeletal disease that is characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture which usually involves the wrist, spine, hip, ribs, pelvis or humerus. In 1994, the WHO proposed a stratified definition of osteoporosis, 1 which was updated in 2008, 2 that encompassed the concepts of both low bone mass and fracture. According to this classification, there are four general categories: normal, low bone mass (osteopenia), osteoporosis and severe osteoporosis.

Three separate and unrelated issues are briefly addressed in this editorial of the final 2011 issue of JEMDSA, namely, comments on some of the articles the journal hosts, a reminder of our Combined SEMDSA-NOFSA Congress in Cape Town in April 2012, and an invitation to reassess and revisit the aims and objectives of our journal, including its Editorial Board.

Statins have been postulated to affect bone metabolism. We investigated the effects of different doses of simvastatin (1, 5, 10, and 20 mg · kg −1 · d −1 ), atorvastatin (2.5 mg · kg −1 · d −1 ), and pravastatin (10 mg · kg −1 · d −1 ) administered orally for 12 weeks to intact female Sprague-Dawley rats and the effect of 20 mg · kg −1 · d −1 simvastatin in sham-operated and ovariectomized rats on femoral bone mineral density (BMD) and quantitative bone histomorphometry (QBH) and compared them with controls. BMD was decreased by 1 mg · kg −1 · d −1 simvastatin ( P =0.042), atorvastatin ( P =0.0002), and pravastatin ( P =0.002). The effect on QBH parameters differed with different doses of simvastatin (ANOVA, P =0.00012). QBH parameters of both bone formation and resorption were equivalently and markedly increased by 20 mg · kg −1 · d −1 simvastatin in 2 separate groups of intact rats and were reflected by a relatively unchanged BMD. At lower doses, 1 mg · kg −1 · d −1 simvastatin decreased bone formation while increasing bone resorption, as reflected by a marked decrease in BMD. Ovariectomized animals receiving 20 mg · kg −1 · d −1 simvastatin showed no change in BMD relative to the untreated, ovariectomized controls; their increase in bone formation was smaller than in sham-operated rats receiving simvastatin, and there was no change in bone resorption. Dose-response curves of simvastatin for bone formation and resorption differed. These studies indicate that (1) statins decrease BMD in rodents, (2) high-dose simvastatin increases bone formation and resorption, (3) low-dose simvastatin decreases bone formation and increases bone resorption, (4) the effects of simvastatin on QBH differ at different dosages, (5) the effects of simvastatin seen in intact rats are not observed in ovariectomized rats, and (6) simvastatin is unable to prevent bone loss caused by ovariectomy.

This document is an update of the clinical guideline published by the National Osteoporosis Foundation of South Africa (NOFSA) in 2000, which aims to improve the overall efficacy of the diagnosis and management of patients with, or at risk for, osteoporosis. The guideline is not limited to any particular patient group and targets all health care workers. This is a detailed summary, which is cross-referenced to the full guideline and is available on the NOFSA (www.osteoporosis.org.za) and JEMDSA (www. jemdsa.co.za) websites.

A low bone mineral density (BMD) is presently regarded as the most important risk factor for the development of osteoporosis. BMD is a function of peak bone mass attained during growth and subsequent age-related bone loss. BMD can be measured accurately and precisely, although the rate of bone loss is more difficult to assess. When axial BMD was measured, the rate of bone loss was shown to increase by 2- to 4-fold at the menopause. Although this rate varies markedly between individuals, it is symmetrically distributed, which argues against the existence of a subpopulation of fast bone losers. Levels of biochemical markers of bone turnover (e.g. osteocalcin, bone specific alkaline phosphatase, deoxypyridinoline) also increase markedly at the menopause, and individuals with a high turnover tend to lose bone more rapidly. Moreover, since increased bone resorption also results in qualitative changes regardless of BMD, a high bone turnover constitutes an independent risk factor. Currently, large intra-individual variations (10 to 40%) in levels of biochemical markers and assay errors still limit our ability to correctly classify individual patients as fast or slow bone losers. The routine use of these markers as a screening tool to predict the risk of osteoporosis in individuals is of limited value, although their selective use in therapeutic decision-making is more promising.

The International Diabetes Federation (IDF) is a global alliance of diabetes associations that has been promoting diabetes care since 1950. It is an umbrella organisation for over 190 diabetes associations in more than 150 countries, divided into seven regions.

No Abstract. Journal of Endocrinology, Metabolism and Diabetes of South Africa Vol. 11(1) 2006: 7-8

The World Health Organisation (WHO)’s definition of osteoporosis is based on the relationship between low bone mineral density (BMD) and consequent increase in bone fragility and susceptibility to fracture.

In 1990, the Society of Endocrinology Metabolism and Diabetes of South Africa (SEMDSA) and a diverse group of individuals interested in metabolic bone diseases in adults and children, held a combined congress in the Wilderness, a seaside village on the east coast of the Western Cape. The “boneheads” subsequently went on to establish the National Osteoporosis Foundation of South Africa (NOFSA) in 1993. This year, the Western Cape will again host a combined meeting. From 19-22 April, the 15th NOFSA and 47th SEMDSA Congress will be held at the President Hotel in Bantry Bay, Cape Town.

In UMR-106 osteosarcoma cells we found that PTH activated both the cAMP/protein kinase A and the Ca2+-dependent phosphoinositide/protein kinase C (PKC) pathways, but prostaglandin E2 (PGE2) activated only the cAMP pathway. Activation of PKC by the phorbol ester PMA had no effect on cAMP production but enhanced PTH-stimulated cAMP production by 50% or more; the effect on PGE2-induced cAMP was negligible. Inhibition of the α-subunit of the inhibitory guanine nucleotide binding protein (Gi) by pertussis toxin pretreatment also enhanced PTH-mediated cAMP production but had no effect on PGE2-induced cAMP production. These results suggest that although PTH-mediated adenylate cyclase activity is regulated via both the stimulatory (Gs) and inhibitory (Gi) guanine nucleotide binding proteins, only Gs regulates PGE2-mediated adenylate cyclase activity in UMR-106 cells. Costimulation with pertussis toxin and PMA did not increase PTH-stimulated cAMP production above that obtained with PMA alone. This implies a similar target of action for pertussis toxin and PMA, that is, the α-subunit of Gi. The α-subunit of Gi was found to be a substrate for in vitro PKC phosphorylation of membrane fractions from UMR-106 cells, seen as a ±40 kD band on SDS-PAGE. Stimulation of in situ 32P-labeled cells with either PMA or PTH also enhanced incorporation of 32P into the 40 kD band. Using the peptide antisera AS/7 and EC/2, we showed that pertussis toxin-labeled subunits of both Gi1α/Gi2α and Gi3α could be immunoprecipitated, respectively, but immuinoprecipitation of membrane proteins after in situ phosphorylation and stimulation with PMA precipitated only Gi2α. We therefore conclude that modulation of adenylate cyclase activity by phorbol esters in UMR-106 osteosarcoma cells can be ascribed, at least in part, to PKC-mediated phosphorylation of the α-subunit of the Gi2 component of the adenylate cyclase regulatory complex.

The second issue of the new JEMDSA has arrived, and in more than one way sets a new benchmark for what we can expect from our journal in future. It is indeed a bumper issue, larger and more diverse than any previous issue of the journal. It is balanced, both in its representation of the various sections of endocrinology, diabetes and metabolism, and also in its format which includes long and short clinical review articles, case histories, a review of a basic scientific nature, an educational article, comments on a clinical trial, a protocol for debate, and of course, original research papers. Finally, the articles are of high scientific quality, often authored by local experts and opinion leaders in the field.

In the previous issue of the Journal, our readers were informed that SEMDSA had decided, after much deliberation and debate, to sever its decade-long ties with the South African Medical Association, that the Health and Medical Publishing Group was to be replaced with a private publishing house, Medpharm Publications, and that it was now "time to move on..."