Fracture risk following bariatric surgery: a population-based study.

UNLABELLED: The effects of bariatric surgery on skeletal health are poorly understood. We found that bariatric surgery patients are more prone to fracture when compared to the general population. While further studies of fracture risk in this population are needed, bone health should be discussed in bariatric surgery clinics. INTRODUCTION: Bariatric surgery is an increasingly common treatment for medically complicated obesity. Adverse skeletal changes after bariatric surgery have been reported, but their clinical importance remains unknown. We hypothesized that bariatric surgery patients are at increased risk of fracture. METHODS: We conducted a historical cohort study of fracture incidence among 258 Olmsted County, Minnesota, residents who underwent a first bariatric surgery in 1985-2004. Relative fracture risk was expressed as standardized incidence ratios (SIRs), while potential risk factors were evaluated by hazard ratios (HR) obtained from a time-to-fracture regression model. RESULTS: The mean (±SD) body mass index at bariatric surgery was 49.0 ± 8.4 kg/m(2), with an average age of 44 ± 10 years and 82% (212) females. Gastric bypass surgery was performed in 94% of cases. Median follow-up was 7.7 years (range, 6 days to 25 years), during which 79 subjects experienced 132 fractures. Relative risk for any fracture was increased 2.3-fold (95% confidence interval (CI), 1.8-2.8) and was elevated for a first fracture at the hip, spine, wrist, or humerus (SIR, 1.9; 95% CI, 1.1-2.9), as well as for a first fracture at any other site (SIR, 2.5; 95% CI, 2.0-3.2). Better preoperative activity status was associated with a lower age-adjusted risk (HR, 0.4; 95% CI, 0.2-0.8) while prior fracture history was not associated with postoperative fracture risk. CONCLUSIONS: Bariatric surgery, which is accompanied by substantial biochemical, hormonal, and mechanical changes, is associated with an increased risk of fracture.

Modification of anodised aluminium surfaces using a picosecond fibre laser for printing applications.

The use of an ultrafast fibre laser at a wavelength of 1064 nm has allowed the surface modification of anodised aluminium plates coated with a 2 micron thick anodised layer for potential industrial applications. The micro- and nano-scale structuring of the anodised aluminium using picosecond pulses of approximately 25 ps duration at 200 kHz repetition rate was investigated. The interaction of the laser with the substrate created a hydrophilic surface, giving a contact angle of less than 10 degrees. On examination under a Scanning Electron Microscope (SEM), a morphology created due to laser induced spallation was observed. It has been found that these laser processed hydrophilic surfaces revert to a hydrophobic state with time. This has potential for application in the printing industry and offers reusability and sustainability of the process materials. This has been confirmed in initial trials.

The effect of cessation of raloxifene treatment on bone turnover in postmenopausal women.

There is evidence to suggest accelerated bone loss following estrogen cessation. The effect of cessation of raloxifene therapy on bone turnover is unknown. Our aim was to determine the effect of cessation of raloxifene treatment on bone turnover and bone mineral density (BMD) in postmenopausal, osteopenic women. Women aged 50 to 80 years received raloxifene for 96 weeks and were then randomized to continue raloxifene (group 1, n=20) or placebo (group 2, n=20) for a further 96 weeks. A third group (group 3, n=14) received no treatment. Bone turnover markers and bone density (BMD) were measured throughout the study. Raloxifene treatment for 96 weeks resulted in a decrease in bone turnover (PINP by 31%) and an increase in spine BMD (by 2%) but no change in hip BMD for groups 1 and 2. Continuation of raloxifene (group 1) maintained these changes. Following cessation of raloxifene (group 2), bone markers returned to baseline levels (by 120 weeks). Hip BMD was decreased by 2% at 192 weeks compared to baseline. Bone markers in the controls (group 3) remained at the upper limit of the reference range throughout, with decreases in BMD of 2.3% (spine) and 2.8% (hip). Bone loss following cessation of raloxifene therapy at 96 weeks was greater than in the control group, suggesting accelerated bone loss. The beneficial effect on bone turnover of 96 weeks of raloxifene was lost 6 months after cessation of treatment.

Estrogen action on bone marrow osteoclast lineage cells of postmenopausal women in vivo.

UNLABELLED: In bone marrow aspirates from postmenopausal women, systemic estrogen treatment decreased differentiation of mononuclear progenitor cells toward a more mature osteoclast phenotype. This was not associated with changes in surface receptor for proresorptive cytokines. INTRODUCTION: Although mechanisms by which estrogen (E) decreases bone resorption have been extensively studied in rodents, little information is available in humans. METHODS: In bone marrow aspirates from 34 early postmenopausal women randomly assigned to receive 4 weeks of treatment (100 microg/day of transdermal 17beta-estradiol) or no treatment, we assessed osteoclast differentiation and surface receptors using flow cytometry with fluorescent-labeled specific antibodies. RESULTS: E treatment decreased (P < 0.05) the proportion of bone marrow mononuclear cells (BMMNCs) expressing the calcitonin receptor (CTR), a late osteoclast phenotype marker. There was an increase in c-Fms concentration in osteoclast lineage cells (P < 0.05) and in the proportion of BMMNCs expressing TNFR2 (P < 0.05), but there were no significant effects on other surface receptors for proresorptive factors (RANK, TNFR1, TREM2, or OSCAR). Changes in serum CTx and TRAP 5b, markers for bone resorption, correlated directly (P < 0.05) with the proportion of BMMNCs expressing CTR and, for TRAP 5b only, TNFR2 and inversely with c-Fms concentration (all P < 0.05). CONCLUSION: E reduces bone resorption, in part, by decreasing differentiation of BMMNCs into mature osteoclasts. This action cannot be explained by decreased concentrations of surface receptors for proresorptive factors. The roles of increases in c-Fms concentration and the proportion of TNFR2((+)) cells are unclear.

High power tunable femtosecond soliton source using hollow-core photonic bandgap fiber, and its use for frequency doubling.

We report a high power tunable femtosecond soliton-based source using a simple combination of fiber-amplified pulses at 1064 nm and hollow-core photonic bandgap fiber. Compression of 5.5 ps input pulses, strongly chirped by self phase modulation in the amplifier, results in stable 520 fs-soliton formation with 77% conversion efficiency after only 8m propagation in the hollow-core fiber. The Raman self-frequency shift of the solitons was used to provide 33 nm wavelength tuneability. The transform-limited output pulses were frequency doubled using a nonlinear crystal with high conversion efficiency of 60% to demonstrate a femtosecond green laser tunable from 534 nm to 548 nm with 180 nJ pulse energy.

Different effects of raloxifene and estrogen on interleukin-1beta and interleukin-1 receptor antagonist production using in vitro and ex vivo studies.

The increase in lumbar spine BMD in response to Raloxifene (RLX), a selective estrogen receptor modulator, is smaller in magnitude compared to the response to treatment with estradiol (E2). The reasons for this observation are unclear. Estrogen has a potent effect on the production of proinflammatory cytokines which support osteoclastogenic and bone resorption. Therefore the different response to RLX may relate, at least in part, to a difference in the ability of RLX to modulate the production of proinflammatory cytokines which are abundant in the red marrow of the vertebrae. The aim of this study was to determine the effect of RLX and E2 both in vitro and ex vivo on the production of the pro-resorptive cytokine interleukin-1beta (IL-1beta) and its antagonist, interleukin-1 receptor antagonist (IL-1ra). We obtained samples of peripheral blood from (a) 10 untreated postmenopausal women with osteopenia (ages 53 to 72 years, mean 61 years), (b) 15 postmenopausal women (ages 52 to 72 years, mean 63 years) at baseline and after 6 months of RLX therapy (60 mg/day) and (c) 10 postmenopausal women (ages 60 to 75 years, mean 64 years) at baseline and 6 months after a single E2 implant (25 mg). Cultures of whole blood from the untreated women were incubated with RLX or 17beta-E2 at 1 pM, 100 pM, 10 nM and 1 microM concentrations. LPS-stimulated whole blood cultures from the raloxifene- and estradiol-treated women were prepared at baseline and at 6 months. IL-1beta and IL-1ra were measured by ELISA in the conditioned media. In vitro there was a significant dose-dependent decrease in IL-1beta and IL-1ra in response to 17beta-E2 (both P<0.0001) which was not apparent in response to RLX (both P>0.05). In ex vivo cultures from women receiving 6 months treatment with E2 implants, there was a significant decrease in IL-1beta (-36+/-8%, P=0.01) but no significant change in IL-1ra (+29+/-20%, P=0.3). There was no significant change in either IL-1beta or IL-1ra after 6 months RLX therapy (+20+/-14% and +12+/-10%, both P>0.05). We conclude that treatment with RLX, unlike estradiol does not modulate the production of the proinflammatory cytokines IL-1beta and IL-1ra using in vitro or ex vivo whole blood culture methods. This may account, at least in part for the reduced efficacy of RLX therapy compared to estrogen which has been observed in vivo on bone mineral density, bone turnover and reduction in fracture risk.

Device-specific thresholds to diagnose osteoporosis at the proximal femur: an approach to interpreting peripheral bone measurements in clinical practice.

INTRODUCTION: A single T score criterion cannot be universally applied to different peripheral bone measurement devices, since measurements in an identical population result in a tenfold difference in the prevalence of osteoporosis. The use of peripheral devices is increasing in clinical practice, despite the difficulties in interpreting results. We propose the use of two thresholds, which have either 95% sensitivity or 95% specificity, to identify (1) individuals who require treatment or (2) individuals who require no treatment, both based on a peripheral measurement alone, or (3) individuals who require additional central densitometry measurements. METHODS: We recruited 500 postmenopausal women, 100 premenopausal women and 279 women with proximal femoral, vertebral, distal forearm or proximal humeral fractures. All subjects underwent dual energy X-ray absorptiometry (DXA) measurements of the lumbar spine, total hip and distal forearm, quantitative computed tomography (QCT) of the distal forearm and quantitative ultrasound (QUS) of the heel (four devices), finger (two devices), radius and metatarsal. We identified the threshold for each device that identified women without osteoporosis with the same sensitivity (upper threshold set at 95%) as total hip DXA and women with osteoporosis with the same specificity (lower threshold set at 95%) as total hip DXA. Individuals between the two thresholds required additional examination by central densitometry. RESULTS: The correlation between devices varied from 0.173 (QUS finger) to 0.686 (DXA forearm) compared with total hip DXA (P<0.0001). The area under the curve (AUC) between devices varied from 0.604 (QUS finger) to 0.896 (DXA forearm) compared with total hip DXA (P<0.0001). In a population-based cohort (prevalence of osteoporosis 9.8%) the threshold approach appropriately identified between 26% (QUS heel) and 68% (DXA forearm) of subjects in whom a treatment decision could be made without additional central DXA with 95% certainty. In a fracture cohort (prevalence of osteoporosis 36%) between 16% (QUS finger) and 37% (QCT forearm) of subjects were appropriately identified. CONCLUSION: The threshold approach to interpreting peripheral bone measurements enables a substantial number of individuals with either normal bone mineral density (BMD) or osteoporosis to be selected and treated appropriately.

Effect of feeding on bone turnover markers and its impact on biological variability of measurements.

Bone turnover markers are subject to day-to-day and within-day variability, which may influence clinical interpretation. We examined the effect of fasting vs. feeding on the concentration and between-day variability of several markers. Twenty healthy premenopausal women were studied on 10 consecutive weekdays. Subjects were studied either in the fasting (no breakfast) or fed (breakfast at 08:00 h) state on alternate days, and were randomized to begin either fasting or fed. Two hour urine collections were obtained each day between 08:00 h and 10:00 h, and blood samples were collected daily at 09:00 h. The N-telopeptide cross-link of type I collagen in urine (uNTX) and serum (sNTX), the C-telopeptide in urine (uCTX) and serum (sbetaCTX), and immunoreactive free deoxypyridinoline (uifDPD) in urine were measured as resorption markers. Procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), and bone alkaline phosphatase (bone ALP) were measured as formation markers. All bone formation and resorption markers were significantly lower in the fed state with the exception of bone ALP. The magnitude of the decrease ranged from 3.8 +/- 0.9% for PINP (p < 0.0001) to 17.8 +/- 2.6% (p < 0.0001) for sbetaCTX. Measurement variability was partitioned into analytical variability based on replicate assays (CV(a)) and within-subject variability (CV(i)). The CV(i) was greater (p < 0.05) for some markers in the fasting state (uifDPD, uNTX, and sNTX) but greater in the fed state for other markers (OC and sbetaCTX). In conclusion, the clinical impact of feeding vs. fasting is small with the exception of sbetaCTX; however, in clinical practice, collection of samples in the fasting state may be necessary to minimize the unpredictable effects of feeding. The mechanism of the acute effect of feeding on bone turnover remains uncertain.

Glucocorticoid-induced osteoporosis.

Glucocorticoids remain a key component in the management of many inflammatory disorders but the adverse consequences, especially on bone, can be devastating. The incidence of glucocorticoid-induced osteoporosis (GIO) may be as high as 50% after 6 months' treatment with steroids. This manifests itself as a 30 to 400% increase in the incidence of low trauma fractures. The incidence rates can be even greater in specific clinical settings such as following organ transplantation. The pathogenesis of glucocorticoid-induced osteoporosis remains complex and perplexing.The concomitant prescription of bone-active drugs for the prevention and treatment of GIO in the United Kingdom population remains low, despite the availability of effective therapies. In addition, there remain many unanswered questions about the pathogenesis of GIO and clinical management. These include identification of the optimum bone mineral density threshold at which to intervene with bone-active drugs, the dose or duration of exposure to steroid therapy that warrants intervention, and the demonstration of the efficacy of fracture prevention for different bone-active drugs or for a combination of these drugs.

Preservation of sight in diabetes: developing a national risk reduction programme.

BACKGROUND: Early treatment for diabetic retinopathy is effective at saving sight, but dependent on pre-symptomatic detection. Although 60% of people with diabetes have their eyes examined annually, few UK health authorities have systematic programmes that meet the British Diabetic Association's standards for sensitivity (> 80%) and specificity (> 95%). Screening is generally performed by general practitioners and optometrists, with some camera-based schemes, operated by dedicated staff. The National Screening Committee commissioned a group to develop a model and cost estimates for a comprehensive national risk-reduction programme. OPHTHALMOSCOPY: Evidence indicates that direct ophthalmoscopy using a hand-held ophthalmoscope does not give adequate specificity and sensitivity, and should be abandoned as a systematic screening technique. Indirect ophthalmoscopy using a slit lamp is sensitive and specific enough to be viable, and widespread availability in high street optometrists is an advantage, but the method requires considerable skill. PHOTOGRAPHIC SCHEMES: The principal advantage of camera-based screening is the capturing of an image, for patient education, review of disease progression, and quality assurance. Digital cameras are becoming cheaper, and are now the preferred option. The image is satisfactory for screening and may be transmitted electronically. With appropriate training and equipment, different professional groups might participate in programme delivery, based on local decisions. COST ISSUES: Considerable resources are already invested in ad hoc screening, with inevitable high referral rates incurring heavy outpatient costs. Treatment for advanced disease is expensive, but less likely to be effective. The costs of a new systematic screening and treatment programme appear similar to current expenditure, as a result of savings in treatment of late-presenting advanced retinopathy. CONCLUSION: A systematic national programme based on digital photography is proposed.

The role of bone turnover markers and risk factors in the assessment of osteoporosis and fracture risk.

The clinical evaluation of osteoporosis in individual patients involves confirmation of the diagnosis, the investigation of secondary causes of osteoporosis and the evaluation of subsequent fracture risk. Optimum clinical assessment involves bone mineral densitometry with the treatment thresholds modified by clinical risk factors for individual patients. Bone turnover markers and clinical risk factors can be used to identify patients at risk of osteoporotic fracture and those who have secondary osteoporosis. Risk assessment should involve the evaluation of absolute rather than relative risk. Further work is required to improve the integration of clinical risk factors, bone turnover markers and bone densitometry into appropriate models to enable the assessment of the absolute risk of fracture for individual patients.

Rapid assessment of gestational age at birth.

A simple scoring system based on skin colour, skin texture, breast development, and ear firmness that can be performed even in an ill baby without manipulation or movement enables gestational age to be estimated to within +/- 15 days (95% confidence limits) at any time in the first 2 days of life. More complex techniques only marginally improve this estimate.