Boning up on osteoporosis - current thinking on management

No Abstract. South African Medical Journal Vol. 96(7) 2006: 604-60

The role of osteoanabolic agents in the management of patients with osteoporosis

Reducing fracture risk is the objective of osteoporosis treatment. Bone-forming osteoporosis drugs increase bone mass, restore bone microarchitecture, and reduce fracture risk more effectively than oral bisphosphonates, providing strong justification for the use of these agents as the initial therapy or after anti-remodeling agents in patients at very high risk of fracture. At the end of a 12-to-24-month course of osteoanabolic therapy, transitioning to a potent anti-remodeling agent maintains and enhances the treatment benefit. This review describes the clinical applications of osteoanabolic therapy for osteoporosis

Reflectance Spectra Analysis Algorithms for the Characterization of Deposits and Condensed Traces on Surfaces

Identification of particulate matter and liquid spills contaminations is essential for many applications, such as forensics, agriculture, security, and environmental protection. For example, toxic industrial compounds deposition in the form of aerosols, or other residual contaminations, pose a secondary, long-lasting health concern due to resuspension and secondary evaporation. This chapter explores several approaches for employing diffuse reflectance spectroscopy in the mid-IR and SWIR to identify particles and films of materials in field conditions. Since the behavior of thin films and particles is more complex compared to absorption spectroscopy of pure compounds, due to the interactions with background materials, the use of physical models combined with statistically-based algorithms for material classification, provides a reliable and practical solution and will be presented

FACTS-international year 2

Summary Objectives:  To compare alendronate 70 mg once weekly (OW) with risedronate 35 mg OW with respect to change in bone mineral density (BMD), biochemical markers and upper gastrointestinal (UGI) tolerability over 24 months. Methods:  This was a 12-month extension to the Fosamax® Actonel® Comparison Trial international study (FACTS). Postmenopausal women with osteoporosis randomly assigned to either alendronate 70 mg OW or risedronate 35 mg OW for the 12-month base study continued taking the same double-blind study medication. Efficacy measurements were BMD at the hip trochanter, lumbar spine, total hip, and femoral neck and levels of four bone turnover markers at 24 months. The primary hypothesis was that alendronate would produce a greater mean per cent increase from baseline in hip trochanter BMD at 24 months. Results:  Trochanter BMD increased significantly from baseline to month 24 in both groups, with a significantly larger increase with alendronate: adjusted mean treatment difference of 1.50% (95% confidence interval: 0.74%, 2.26%; p < 0.001). Similar results were seen at all BMD sites. Significant geometric mean per cent decreases (p < 0.001) from baseline were seen for all four bone turnover markers in both groups, with significantly larger decreases (p < 0.001) with alendronate: adjusted mean treatment differences ranged from 8.9% to 25.3%. No significant differences were seen in incidence of UGI or other adverse events. Conclusions:  Alendronate 70 mg OW yielded significantly greater BMD gains and larger decreases in bone turnover marker levels than risedronate 35 mg OW over 24 months, with no difference in UGI tolerability

Femoral and vertebral strength improvements in postmenopausal women with osteoporosis treated with denosumab

In the randomized, placebo-controlled FREEDOM study of women aged 60 to 90 years with postmenopausal osteoporosis, treatment with denosumab once every 6 months for 36 months significantly reduced hip and new vertebral fracture risk by 40% and 68%, respectively. To gain further insight into this efficacy, we performed a nonlinear finite element analysis (FEA) of hip and spine quantitative computed tomography (QCT) scans to estimate hip and spine strength in a subset of FREEDOM subjects (n=48 placebo; n=51 denosumab) at baseline, 12, 24, and 36 months. We found that, compared with baseline, the finite element estimates of hip strength increased from 12 months (5.3%; p<0.0001) and through 36 months (8.6%; p<0.0001) in the denosumab group. For the placebo group, hip strength did not change at 12 months and decreased at 36 months (-5.6%; p<0.0001). Similar changes were observed at the spine: strength increased by 18.2% at 36 months for the denosumab group (p<0.0001) and decreased by -4.2% for the placebo group (p=0.002). At 36 months, hip and spine strength increased for the denosumab group compared with the placebo group by 14.3% (p<0.0001) and 22.4% (p<0.0001), respectively. Further analysis of the finite element models indicated that strength associated with the trabecular bone was lost at the hip and spine in the placebo group, whereas strength associated with both the trabecular and cortical bone improved in the denosumab group. In conclusion, treatment with denosumab increased hip and spine strength as estimated by FEA of QCT scans compared with both baseline and placebo owing to positive treatment effects in both the trabecular and cortical bone compartments. These findings provide insight into the mechanism by which denosumab reduces fracture risk for postmenopausal women with osteoporosis

Cerebral blood flow and behavioural effects of caffeine in habitual and non-habitual consumers of caffeine: A near infrared spectroscopy study

Caffeine has been shown to modulate cerebral blood flow, with little evidence of tolerance to these effects following habitual use. However, previous studies have focused on caffeine levels much higher than those found in dietary servings and have compared high caffeine consumers with low consumers rather than 'non-consumers'. The current placebo-controlled double-blind, balanced-crossover study employed near infrared spectroscopy to monitor pre-frontal cerebral-haemodynamics at rest and during completion of tasks that activate the pre-frontal cortex. Twenty healthy young habitual and non-habitual consumers of caffeine received 75mg caffeine or placebo. Caffeine significantly decreased cerebral blood flow but this was subject to a significant interaction with consumption status, with no significant effect being shown in habitual consumers and an exaggerated effect in non-habitual consumers. These findings suggest that caffeine, at levels typically found in a single dietary serving, is able to modulate cerebral blood flow but these effects are subject to tolerance

An early Phase II randomised controlled trial testing the effect on persecutory delusions of using CBT to reduce negative cognitions about the self: the potential benefits of enhancing self confidence

Background Research has shown that paranoia may directly build on negative ideas about the self. Feeling inferior can lead to ideas of vulnerability. The clinical prediction is that decreasing negative self cognitions will reduce paranoia. Method Thirty patients with persistent persecutory delusions were randomised to receive brief CBT in addition to standard care or to standard care (ISRCTN06118265). The six session intervention was designed to decrease negative, and increase positive, self cognitions. Assessments at baseline, 8 weeks (posttreatment) and 12 weeks were carried out by a rater blind to allocation. The primary outcomes were posttreatment scores for negative self beliefs and paranoia. Secondary outcomes were psychological well-being, positive beliefs about the self, persecutory delusions, social comparison, self-esteem, anxiety, and depression. Results Trial recruitment and retention were feasible and the intervention highly acceptable to the patients. All patients provided follow-up data. Posttreatment there was a small reduction in negative self beliefs (Cohen's d = 0.24) and a moderate reduction in paranoia (d = 0.59), but these were not statistically significant. There were statistically significant improvements in psychological well-being (d = 1.16), positive beliefs about the self (d = 1.00), negative social comparison (d = 0.88), self-esteem (d = 0.62), and depression (d = 0.68). No improvements were maintained. No adverse events were associated with the intervention. Conclusions The intervention produced short-term gains consistent with the prediction that improving cognitions about the self will reduce persecutory delusions. The improvement in psychological well-being is important in its own right. We recommend that the different elements of the intervention are tested separately and that the treatment is lengthened

Epidemiology and heritability of Major Depressive Disorder, stratified by age of onset, sex, and illness course in Generation Scotland:Scottish Family Health Study (GS:SFHS)

The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)