Fracture risk in diabetic elderly men: the MrOS study

Aims/hypothesis

Diabetes mellitus is associated with increased fracture risk in women but few studies are available in men. To evaluate the relationship between diabetes and prospective non-vertebral fractures in elderly men, we used data from the Osteoporotic Fractures in Men (MrOS) study.

Methods

The MrOS enrolled 5,994 men (aged ≥65 years). Diabetes (ascertained by self-report, the use of medication for diabetes or an elevated fasting glucose level) was reported in 881 individuals, 80 of whom were using insulin. Hip and spine bone mineral density (BMD) was measured using dual x-ray absorptiometry (DXA). After recruitment, the men were followed for incident non-vertebral fractures using a triannual (3 yearly) questionnaire for an average of 9.1 (SD 2.7) years. The Cox proportional hazards model was used to assess the incident risk of fractures.

Results

In models adjusted for age, race, clinic site and total hip BMD, the risk of non-vertebral fracture was higher in men with diabetes compared with normoglycaemic men (HR 1.30, 95% CI 1.09, 1.54) and was elevated in men using insulin (HR 2.46, 95% CI 1.69, 3.59). Men with impaired fasting glucose did not have a higher risk of fracture compared with normoglycaemic men (HR 1.04, 95% CI 0.89, 1.21). After multivariable adjustment, the risk of non-vertebral fracture remained higher only among men with diabetes who were using insulin (HR 1.74, 95% CI 1.13, 2.69).

Conclusions/interpretation

Men with diabetes who are using insulin have an increased risk of non-vertebral fracture for a given age and BMD.     

Separate impact of metabolic syndrome and altered glucose tolerance on early markers of vascular injuries

ObjectiveWe investigated the separate impact of metabolic syndrome (MS) and altered glucose tolerance on early markers of vascular injuries.MethodsIntima-media thickness (IMT) and Pulse Wave Analysis (PWA), were evaluated in 132 overweight or obese subjects, with (MS⁺) or without (MS^?) MS; subjects were further classified as normotolerant (NT) or with altered glucose tolerance (AGT) according to a 2 h oral glucose tolerance test (OGTT).ResultsIn MS⁺ patients, IMT was higher than in the MS^? group, and PWA revealed higher Augmentation Pressure (Aug, the contribution that wave reflection makes to systolic arterial pressure) and lower subendocardial viability ratio (SEVR, an estimate of myocardial perfusion). When analyzed according to glucose tolerance, IMT was higher in MS⁺NT subjects and AGT patients with and without MS, vs. MS^?NT subjects. Logistic regression modeling showed that both AGT and MS were independently associated with increased IMT. However, only MS remained associated with IMT after adjustment for age. SEVR was reduced only in MS⁺ patients, independently of glucose tolerance. In both groups, Aug and AugI were higher in the AGT group, but the correlation with 2 h-plasma glucose disappeared when corrected for age.ConclusionBoth MS and AGT altered IMT, but the effect of AGT disappears when age is added to the multiple regression model. In contrast, arterial stiffness was affected differently in the two categories: in subjects with MS, the subendocardial viability ratio (an estimate of myocardial perfusion) was impaired, while in subjects with AGT, both Aug and AugI were increased. These data suggest that applying the definition of MS might help to better characterize cardiovascular risk in subjects with altered glucose tolerance or obesity.     

Finding my own way: an fMRI single case study of a subject with developmental topographical disorientation

Developmental topographical disorientation (DTD) causes impaired spatial orientation and navigation from early childhood with no evidence of cerebral damage. Using fMRI and a landmark sequencing task, we investigated the hypothesis that Dr Wai’s abnormal cerebral activation pattern was related to his peculiar behavioral profile. Although Dr Wai was able to correctly perform landmark sequencing, he showed a lack of activity in regions activated in all control subjects and activity in areas that were not activated in any control subject. These results are discussed in light of cognitive and functional model of navigation, with relevant implications for DTD physiology.     

手术在治疗先天性脉管畸形中的作用

手术是脉管性病变治疗的一种手段,其主要作用是与放射治疗及各种药物治疗协同作用。对于血管瘤患者,手术仅限于普萘洛尔治疗无效,出现并发症及位于眼部的病变。整形手术可使血管瘤消退后遗留的面部畸形得到改善。对于一些范围较小的局灶性病变,手术往往可以取得满意的效果;对于巨大、多发的血管瘤,手术治疗往往作用有限,常常为减瘤术。手术患者一般在术前均经过栓塞硬化治疗,这样可以大大减少术中出血。手术无法治愈脉管性疾病,是一种辅助     

Intensive Glycemic Control and Thiazolidinedione Use: Effects on Cortical and Trabecular Bone at the Radius and Tibia

Factors that contribute to bone fragility in type 2 diabetes are not well understood. We assessed the effects of intensive glycemic control, thiazolidinediones (TZDs), and A_1C levels on bone geometry and strength at the radius and tibia. In a substudy of the Action to Control Cardiovascular Risk in Diabetes trial, peripheral quantitative computed tomographic (pQCT) scans of the radius and tibia were obtained 2 years after randomization on 73 participants (intensive n = 35, standard n = 38). TZD use and A_1C levels were measured every 4 months during the trial. Effects of intervention assignment, TZD use, and A_1C on pQCT parameters were assessed in linear regression models. Intensive, compared with standard, glycemic control was associated with 1.3 % lower cortical volumetric BMD at the tibia in men (p = 0.02) but not with other pQCT parameters. In women, but not men, each additional year of TZD use was associated with an 11 % lower polar strength strain index (SSIp) at the radius (p = 0.04) and tibia (p = 0.002) in models adjusted for A_1C levels. In women, each additional 1 % increase in A_1C was associated with an 18 % lower SSIp at the ultradistal radius (p = 0.04) in models adjusted for TZD use. There was no consistent evidence of an effect of intensive, compared with standard, glycemic control on bone strength at the radius or tibia. In women, TZD use may reduce bone strength at these sites. Higher A_1C may also be associated with lower bone strength at the radius, but not tibia, in women.     

A randomized, placebo-controlled trial of vitamin D supplementation to improve glycaemia in overweight and obese African Americans

Aims: Vitamin D deficiency may increase the risk for type 2 diabetes. African Americans tend to have poor vitamin D status and increased risk of diabetes, but effects of vitamin D supplementation on components of diabetes risk have not been tested in this group. This study was conducted to determine whether vitamin D supplementation improves insulin secretion, insulin sensitivity and glycaemia in African Americans with prediabetes or early diabetes. Methods: In this randomized, placebo‐controlled trial, we examined the effect of 4000 IU/day vitamin D_3, on glycaemia and contributing measures including insulin secretion, insulin sensitivity and the disposition index over 12 weeks in 89 overweight or obese African Americans with prediabetes or early diabetes. Outcome measures were derived from oral glucose tolerance testing. Results: Mean plasma 25‐hydroxyvitamin D was about 40 nmol/l in the placebo and vitamin D groups at baseline and increased to 81 nmol/l with supplementation. Insulin sensitivity decreased by 4% in the vitamin D group compared with a 12% increase in the placebo group (p = 0.034). Insulin secretion increased by 12% in the vitamin D group compared with a 2% increase in the placebo group (p = 0.024), but changes in the disposition index were similar across groups. There was no effect of supplementation on post‐load glucose or other measures of glycaemia. Conclusions: Supplementation with 4000 IU/day vitamin D₃ successfully corrected vitamin D insufficiency and had divergent effects on insulin secretion and sensitivity with no overall effect on disposition index or glycaemia. In this study, vitamin D supplementation for 3 months did not change the pathophysiology of prediabetes in overweight and obese African Americans.     

Meal conditions affect the absorption of supplemental vitamin D3 but not the plasma 25‐hydroxyvitamin D response to supplementation

It is sometimes assumed that dietary fat is required for vitamin D absorption, although the impact of different amounts of dietary fat on vitamin D absorption is not established. This study was conducted to determine whether the presence of a meal and the fat content of the meal influences vitamin D absorption or the 25‐hydroxyvitamin D [25(OH)D] response to supplemental vitamin D₃. Based on earlier studies in rats we postulated that absorption would be greatest in the low‐fat meal group. Sixty‐two healthy older men and women were randomly assigned to one of three meal groups: no meal, high‐fat meal, or low‐fat meal; each was given a monthly 50,000 IU vitamin D₃ supplement with the test breakfast meal (or after a fast for the no‐meal group) and followed for 90 days. Plasma vitamin D₃ was measured by liquid chromatography–mass spectroscopy (LC/MS) before and 12 hours after the first dose; plasma 25(OH)D was measured by radioimmunoassay at baseline and after 30 and 90 days. The mean 12‐hour increments in vitamin D₃, after adjusting for age and sex, were 200.9 nmol/L in the no‐meal group, 207.4 nmol/L in the high‐fat meal group, and 241.1 nmol/L in the low‐fat meal group (p = 0.038), with the increase in the low‐fat group being significantly greater than the increases in the other two groups. However, increments in 25(OH)D levels at 30 and 90 days did not differ significantly in the three groups. We conclude that absorption was increased when a 50,000 IU dose of vitamin D was taken with a low‐fat meal, compared with a high‐fat meal and no meal, but that the greater absorption did not result in higher plasma 25(OH)D levels in the low‐fat meal group.     

A modified direct lateral approach for neck-preserving total hip arthroplasty: tips and technical notes

Tissue-sparing surgery for hip replacement aims to minimize muscle damage and conserve the femoral neck through the use of mini-prostheses. We propose a modification of the classical direct lateral access procedure that preserves the gluteus medius. Further advantages during the surgical phase include limited blood loss, visualization of the entire acetabulum, and sparing of the transverse ligament. Precise implantation is facilitated and normal biomechanics are preserved. The gluteus medius is divided longitudinally between the anterior third and posterior two-thirds to provide access to the gluteus minimus, which is detached from the femoral insertion together with a small portion of the vastus lateralis, forming a flap that exposes the underlying articular capsule. When the femoral head is revealed, a decision is made to either continue with its dislocation directly or to resect it and remove it separately to avoid damaging the gluteus medius during dislocation. Upon removal of the femoral head, with the limb flexed and slightly over-rotated, the acetabulum is completely visible. Limb length is maintained through the use of reference stitches on the gluteus minimus tendon and the proximal insertion of the vastus lateralis. In keeping with the minimally invasive philosophy, only pathological tissue is removed (marginal osteophytes, geodes, joint capsule, cartilage to the point of bleeding and pulvinar). We have performed more than 2,000 implants with this procedure since 1990. Advantages and potential critical points are discussed.     

Treatment of bisphosphonate-related osteonecrosis of the jaws: presentation of a protocol and an observational longitudinal study of an Italian series of cases

The aim of this study was to evaluate the efficacy of a treatment protocol for bisphosphonate-related osteonecrosis of the jaws (BRONJs). We conducted a longitudinal observational non-controlled study in 94 patients with confirmed BRONJ. Treatment was in two phases: supportive (antimicrobial mouth rinses, antibiotics, and anti-inflammatory steroids) to minimise infection and pain before the formation of a bony sequestrum; and surgical plus pharmacological treatment (sequestrectomy with antibiotic prophylaxis) after the sequestrum had developed. We did a Kaplan-Meier analysis (survival curve) to evaluate the time from the initial assessment until the formation of the bony sequestrum (endpoint), and a log-rank (Mantel-Haenszel) test to compare the formation times of the sequestra in men and women. Ninety-one of the 94 patients developed sequestra and were operated on. Three patients were withdrawn from the study because of severe pain and were treated by debridement before the sequestra developed. The results showed that sequestra developed within 15 months in all 91 patients. The Kaplan-Meier analysis showed that the mean time to formation of a sequestrum was 8 months (range 5-11). The difference between the mean time for men (5 months, range 2-8) and women (9 months, range 6-12) was highly significant (p<0.0001). Within the limits of this study, we conclude that by waiting for the formation of bony sequestra while controlling infection and pain, it is possible to do a conservative resection, unless pain is severe or there is a risk of fracture. This non-aggressive approach permits the removal of all necrotic bone, avoids damage to adjacent healthy bone, and does not result in recurrences.