Effect of calcium and vitamin D supplementation on bone mineral density in women aged 65-71 years: a 3-year randomized population-based trial (OSTPRE-FPS).

SUMMARY: The Osteoporosis Risk Factor and Prevention-Fracture Prevention Study (OSTPRE-FPS) was a randomized population-based open trial (n = 593). The supplementation group (n = 287) received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years while the control group (n = 306) received neither supplementation nor placebo. Daily vitamin D and calcium supplementation have a positive effect on the skeleton in ambulatory postmenopausal women. INTRODUCTION: vitamin D deficiency is common in the elderly, and vitamin D levels are associated with low bone mineral density (BMD). The working hypothesis was that vitamin D and calcium supplementation could prevent bone loss in ambulatory postmenopausal women. METHODS: the OSTPRE-FPS was a randomized population-based open trial with a 3-year follow-up in 3,432 women (aged 66 to 71 years). A randomly selected subsample of 593 subjects underwent BMD measurements. The supplementation group (n = 287) received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years while the control group (n = 306) received neither supplementation nor placebo. RESULTS: in the intention-to-treat analysis, total body BMD (n = 362) increased significantly more in the intervention group than in the control group (0.84% vs. 0.19%, p = 0.011). The BMD change differences at the lumbar spine (p = 0.372), femoral neck (p = 0.188), trochanter (p = 0.085), and total proximal femur (p = 0.070) were statistically nonsignificant. Analyses in compliant women (≥ 80% of use) resulted in stronger and statistically significant effects at the total body and femoral regions. CONCLUSION: daily vitamin D and calcium supplementation have a positive effect on the skeleton in ambulatory postmenopausal women with adequate nutritional calcium intake.

Sister's fracture history may be associated with perimenopausal bone fragility and modifies the predictability of fracture risk.

SUMMARY: The present study investigated the effects of first degree relatives' fractures on fracture incidence after the menopause. Sister's, but not other relatives', wrist or hip fracture history was associated with increased risk of fragility fractures after the menopause. This suggests genetic predisposition to bone fragility among postmenopausal women. OBJECTIVE: The aim of the present study was to investigate the association between first degree relatives' fractures and perimenopausal bone fragility. MATERIALS AND METHODS: The study sample of 971 perimenopausal women was extracted from randomly selected Kuopio Osteoporosis Risk Factor and Prevention cohort and measured with dual X-ray absorptiometry in femoral neck (FN) in baseline (1989-1991), in 5 years (1994-97), and in 10 years (1999-2001). All low-trauma energy fractures during the 10-year follow-up were recorded based on self-reports and validated from medical records. First degree relatives' history of life-time hip and wrist fractures (exact classification or trauma energy not specified) was questioned by postal inquiries. RESULTS: There was a significant correlation between fathers' vs. brothers' and mothers' vs. sisters' fractures (p < 0.01 in Pearson bivariate correlations). Sister's, but not mother's, father's, or brother's wrist and hip fractures were associated with significantly lowered 10-year fragility fracture-free survival rate (HR = 0.56, p = 0.006). Sisters' or other relatives' fractures were not associated with FN bone loss rate or bone mineral density (BMD) in the follow-up measurements (p = NS in ANCOVA). The predictive power of BMD for fragility fractures differed according to sisters' fracture history: Baseline FN T score predicted fracture-free survival only among women without sisters' fracture history (HR 0.62, p < 0.001 vs. women with sisters' fracture in Cox regression). CONCLUSIONS: In conclusion, sisters' fracture history is associated with 10-year fracture-free survival in perimenopausal women but not with BMD or its changes. Predictability of fragility fracture risk with BMD may depend on sister's fracture history. This may indirectly suggest genetic predisposition to bone fragility independently of BMD.

Association between functional capacity tests and fractures: an eight-year prospective population-based cohort study.

UNLABELLED: This study of postmenopausal women (n=2,928) with an eight-year follow-up revealed that impairment in functional status associated with the increased fracture risk. The standing-on-one-foot and grip strength tests and a question about self-assessed ability to move can be used to identify women with a high risk of suffering a fracture. INTRODUCTION: Poor functional status has pointed to associate with injurious falls and consequent fractures. Our aim was to define association between functional capacity and fractures. METHODS: This study was based on the Osteoporosis Risk Factor and Prevention Study (OSTPRE). A total of 2,928 postmenopausal women took part in the functional capacity and muscle strength tests. The duration of fracture follow-up varied from 6.43 to 9.86 (mean 8.37) years and the first fracture was the end-point event for the statistical analyses. All analyses were done with Cox-regression. RESULTS: A total of 261 end-point fractures occurred. In multivariate analysis the inability to stand-on-one-foot for 10 seconds increased the risk of hip fracture (hazard ratio with 95% CI) 9.11-fold (1.98-42.00). Decreased grip strength associated with 1.05-fold (1.01-1.09) increased risk of hip fractures. Low leg extension strength associated with 1.02-fold (1.00-1.03) higher risk for all fractures. The self-assessed ability to walk less than 100 meters at baseline increased the risk of ankle 2.36-fold (1.10-5.08), hip 11.57-fold (2.73-49.15) and clinical vertebral fractures 3.85-fold (1.45-10.22). CONCLUSION: According to these results the standing-on-one-foot less than 10 seconds, grip strength and a question about ability to walk less than 100 meters may help to predict postmenopausal fractures.

Red blood cell and tissue water content in experimental thermal injury.

UNLABELLED: Oedema formation and changes in local blood flow are known phenomena in burns. The relationship between these two is not clearly described. The aim of this study was firstly to examine both the contents of red blood cells and tissue water in skin and subcutaneous fat after experimental burns of different depths in pigs, and secondly, to confirm our recent findings of the increased dielectric constant of skin and subcutaneous fat reflecting considerable oedema formation, especially in fat after thermal injury. METHODS: Superficial, partial and full thickness contact burns were created to pigs and followed for 24h. Radioactive Cr-51 labelling of red cells was used to estimate the number of red cells in tissue, and the absolute amount of water was determined by lyophilization. RESULTS: A decreased number of labelled red cells in skin and an increase in tissue water in subcutaneous fat were found regardless of burn depth. The highest water amount in fat was found in the partial thickness burns. CONCLUSION: All burn depths resulted in a diminished number of labelled red blood cells in skin and a significant increase in the absolute water amount in subcutaneous fat at 24h post injury. The findings in fat support our recent findings of highly elevated dielectric constants measured by the new in vivo method of dielectric measurements.

Apelin, orexin-A and leptin plasma levels in morbid obesity and effect of gastric banding.

UNLABELLED: Maintenance of human energy homeostasis is regulated by a complex network. Peptides secreted from the gastrointestinal tract (GI) are signaling to the brain and other organs initiating or terminating food intake and energy expenditure. In the present study we investigated basal plasma levels of apelin, orexin-A, and leptin in morbid obese patients. In addition, we measured in a subgroup of these patients in the same individual orexin-A and leptin plasma levels one year after gastric banding surgery. METHODS: Basal plasma values were determined in obese patients (BMI=48+/-1 kg/m2n=32) after an overnight fast and compared to healthy, normal weighted (BMI=22+/-2 kg/m2n=12) controls. In addition, blood samples were collected in a subgroup of patients (BMI=48+/-1 kg/m2n=8) the day before surgery and 1 year after the operation. Apelin, orexin-A, and leptin levels were analysed using ELISAs. RESULTS: One year after the operation obese patients significantly lost weight (from 48+/-2 kg/m2 to 39+/-2 kg/m2; p<0,001). Apelin, orexin-A and leptin levels in obese patients were significantly higher compared to control individuals (736+/-50 pg/ml vs. 174+/-14 pg/ml, p<0.0001; 75.3+/-24.1 pg/ml vs. 0.8+/-0.4 pg/ml, p<0.0001; 79.0+/-2.4 ng/ml vs. 5.8+/-0.8 ng/ml, p<0.0001, respectively). Apelin and leptin plasma concentrations also correlated significantly with BMI (r=0.769, p<0.0001; r=0.778; p<0.0001, respectively), while orexin-A correlation was rather weak (r=0.335, p<0.03). No difference between pre- and post-operative orexin-A levels was observed, while leptin plasma levels significantly decreased from 45.1+/-5.4 ng/ml to 27.3+/-6.0 ng/ml (p=0.015). CONCLUSIONS: Apelin, orexin-A, and leptin plasma levels correlated positively with the BMI. One year after gastric banding with significant loss in BMI basal plasma levels of leptin decreased, while orexin-A remained unchanged.

Microdialysis for detection of dynamic changes in tissue histamine levels in experimental thermal injury.

Histamine is an important mediator contributing to oedema formation after thermal injury. Tissue histamine concentrations have been previously determined by analyzing tissue biopsies. The microdialysis method enables continuous collection of samples from the extracellular tissue fluid. In this experimental burn study on pigs samples from the extracellular fluid for histamine analysis were collected from superficial, partial thickness and full thickness burn sites during a 24-h period. There was a burn depth-related increase in histamine concentrations during the first 2 h post injury. Deep burns induced a more profound initial increase in tissue histamine concentration than the partial thickness and superficial burns. Histamine concentrations at all burn sites declined until 12 h post injury. There was a second rise in tissue histamine concentrations between 12 and 24 h post injury without a rise in plasma histamine concentrations. Histamine concentrations at all burn sites were higher than at the non-burned control sites. The microdialysis technique is an easily applicable method of collecting on-line samples from burned tissue. This method provides a useful tool in investigating the effects of different treatment modalities on the secretion of substances into interstitial fluid within burned tissue.

The progression of burn depth in experimental burns: a histological and methodological study.

UNLABELLED: This study was designed to create a reproducible model for experimental burn wound research in pigs. Previously, the thicker paraspinal skin has been used. We used the more human-like ventral skin to create burns of different depths. Contact burns were created to 11 pigs using a brass plate heated to 100 degrees C in boiling water. Different contact times were used to create burns of different depths. In pigs 1-6, the follow-up time was 72 h and in pigs 7-11 24 h. Burn depth was determined by histology. Histologically, samples were classified into five anatomical layers: epidermis, upper one-third of the dermis, middle third of the dermis, deepest third of the dermis and subcutaneous fat. The location of both thromboses and burn marks were evaluated, respectively. The 1 s contact time lead to a superficial thermal injury, 3 s to a partial thickness and 9 s to a full thickness injury. A progression of burn depth was found until 48 h post-injury. The intra-observer correlation after repeated histological analyses of burn depths by the same histopathologist and the repeatability of burn depth creation yielded kappa coefficients 0.83 and 0.92, respectively. CONCLUSION: a reproducible burn model for further research purposes was obtained.

Heat shock preconditioning and eicosanoid pathways modulate caspase 3-like activity in superficially injured isolated guinea pig gastric mucosa.

BACKGROUND: After superficial mucosal injury, the disturbed gastric epithelial continuity is restored by cellular migration. Caspase-3 is an enzyme responsible for the execution of stress-induced apoptosis. Interestingly, heat shock proteins (Hsp) including Hsp60 are capable of modulating caspase-3 activity. Interestingly, we have demonstrated that heat shock preconditioning upregulates Hsp synthesis and inhibits restitution and cell proliferation via mechanisms related to de novo protein synthesis and eicosanoid pathways, both of which are crucial in the regulation of apoptosis and gastric mucosal defense systems. AIMS: To assess whether caspase-3 activity is affected by heat shock preconditioning and associated pharmacological modulations after standard superficial injury to allow development of cytoprotective strategies. METHODS: Guinea pig gastric mucosae were mounted and perfused in paired Ussing chambers. After heat shock (HS) preconditioning (42 degrees C) for 30 min, a superficial injury was induced (1.25 mol/l NaCl) followed by 3 h recovery. For mechanistic studies, the mucosa was exposed to 30 micromol/l arachidonic acid (AA) as a substrate for eicosanoid pathways, to 50 micromol/l quercetin (Q) to inhibit lipoxygenases, to 50 micromol/l indomethacin (In) to inhibit cyclo-oxygenases, or to 150 micromol/l cycloheximide (CHX) to inhibit de novo protein synthesis. After the experiment, the mucosa was prepared for analysis of caspase-3 activity. Hsp60 expression was analyzed to monitor the induction of heat shock response. RESULTS: HS upregulated Hsp60 expression, indicating induction of the heat shock response without an effect on basal caspase-3 activity. Superficial injury itself did not affect caspase-3 activity nor Hsp60 synthesis. In all the experiments, exposure to CHX abolished caspase-3 activity and Hsp60 synthesis. AA+Q increased, Q decreased, while In+AA and In+AA+Q abolished caspase-3 activity independent of alterations in Hsp60 synthesis. Upon exposure to In+Q, HS decreased caspase-3 activity and upregulated Hsp60 synthesis. CONCLUSION: Caspase-3 activity in isolated guinea pig gastric mucosa is regulated by mechanisms dependent on de novo protein synthesis and eicosanoid pathways but is not strictly related to Hsp synthesis. Upon modulation of the eicosanoid pathways, HS may be utilized to simultaneously decrease caspase-3 activity and increase Hsp synthesis. Modulations of the eicosanoid pathways may be utilized to reduce caspase-3 activity also upon normothermic conditions suggesting a novel mechanism by which caspase-3 is regulated in the gastric mucosa.

Calcaneal ultrasound predicts early postmenopausal fractures as well as axial BMD. A prospective study of 422 women.

Low calcaneal ultrasound measurement (quantitative ultrasound, QUS) has been shown to predict fractures in elderly women. However, only a few studies have examined its ability to predict perimenopausal and early postmenopausal fractures. We conducted a prospective population-based cohort study to assess the capability of QUS as compared to axial BMD measurement to predict early postmenopausal fractures at that age. Four hundred and twenty-two women (mean age 59.6, range 53.7-65.3) from the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) were randomly chosen to undergo a calcaneal ultrasound measurement. In all, 9.4% of these women were premenopausal at the time of measurement. Thirty-two follow-up fractures were reported during the mean follow-up of 2.6 years (SD 0.7). These were validated with patient record perusal. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were significantly lower among women with than without fracture ( P-values 0.028, 0.001 and 0.001, respectively). Mean T-score adapted from SI was -1.5 (95% CI -1.7 to -1.2) for fracture group and -1.0 (95% CI -1.1 to -0.9) for the non-fracture group. All QUS measurements predicted fractures even after adjusting for age, weight, height, previous fracture history, femoral neck BMD and use of hormone replacement therapy according to Cox regression. The adjusted hazard ratios (HR, 95% confidence interval) of a follow-up fracture for a 1 SD decrease were 1.80 (1.27-2.56), 1.72 (1.21-2.45) and 1.43 (1.01-2.03) for SOS, SI and BUA, respectively. Similarly, the adjusted HR for a 1 SD decrease of spinal BMD was 1.27 (0.85-1.94) and for that of femoral neck BMD 1.14 (0.78-1.70). In receiver operator analyses, the area under the curve (AUC) was greatest for QUS measurements: SOS (AUC=0.68), stiffness (AUC=0.67), BUA (AUC=0.62) and least for lumbar BMD (AUC=0.56), while and femoral neck BMD (AUC=0.59). The difference between AUCs was statistically significant between SI and lumbar BMD ( P=0.02, Duncan's P=0.07). We conclude that low calcaneal QUS predicts early postmenopausal fractures as well as or even better than axial BMD.

A pitfall of metaiodobenzylguanidine scan: paraganglioma in close proximity to adrenocortical adenoma.

We report a potential pitfall of 123I-metaiodobenzylguanine (MIBG) scan. Magnetic resonance imaging performed for other reasons, showed 2.5 cm tumor in the left adrenal gland. On questioning patient had episodic palpitations, flushing and hypertension suggestive of pheochromocytoma. Urinary metanephrine level was of borderline value but serum chromogranin A level was clearly elevated. 123I-MIBG scan showed accumulation of the tracer in the upper left abdomen and the finding was suspected to be intra-adrenal pheochromocytoma. During operation two separate tumors, adrenocortical adenoma in the left adrenal gland, and another smaller, extra-adrenal paraganglioma locating very close to the adenoma, were found. Thus the positive MIBG finding was caused by a paraganglioma with the concurrent presentation of nonfunctioning adrenocortical adenoma.

Sauna-bathing with sutures. A prospective and randomised study.

BACKGROUND AND AIMS: Bathing in sauna is a Finnish habit with numerous beliefs and traditions. One belief has been that one is not allowed to go to sauna postoperatively with sutures. This belief is in practically every patient information sheet in Finland on postoperative wound care. There is no scientific proof of the harmfulness of sauna-bathing with sutures and no articles on the matter, either. The aim of this study was to evaluate whether sauna-bathing has a negative impact on wound healing. MATERIALS AND METHODS: Prospective, randomised study with 79 patients scheduled for an elective hernioplasty in a day care surgical department. The other group was advised to go to sauna from 3rd postoperative day on, and for the other group, sauna was prohibited until sutures were removed. RESULTS: There was no differences in wound healing between two groups. CONCLUSION: There is no reason to prohibit sauna-bathing with sutures in this patient group.

The effect of photodynamic therapy on rat urinary bladder with orthotopic urothelial carcinoma.

OBJECTIVE: To assess the effect of whole-bladder photodynamic therapy (PDT) on a rat model with orthotopic superficial bladder cancer, as PDT is an alternative intravesical therapy for treating superficial bladder cancer, based on an interaction between a photosensitizer and light energy to induce oxygen radicals that destroy tissue by lipid peroxidation. MATERIALS AND METHODS: In all, 76 female Fischer F344 rats were inoculated intravesically with AY-27 tumour cells. After establishing superficial tumour, 24 rats were treated with PDT using aminolaevulinic acid (ALA)-induced protoporphyrin IX as a photosensitizer, and a continuous-wave argon pumped-dye laser (638 nm). At 4 h after intravenous (300 mg/kg) or intravesical (100 mg/mL) administration of ALA the bladders were intravesically exposed to a 40 J/cm(2) light dose; 12 rats received no ALA but were exposed to the same light dose. Before administering ALA, urine cytology samples were taken for analysis. At 3 or 21 days the treated rats were killed and morphological changes in the bladder walls analysed by light microscopy. Forty rats served as controls to examine the presence of tumour. RESULTS: The tumour established in 33 of 40 rats (83%) in the controls, but after PDT with intravesical ALA there was carcinoma in only in one of 12 (P < 0.001, Pearson's chi(2) test). After PDT with intravenous ALA there was carcinoma in five of 11 rats (P = 0.063, Pearson's chi2 test). In the control group of 12 rats receiving only light energy there was carcinoma in three (P = 0.001, Pearson's chi(2) test). Histologically, at 3 days after PDT there was only mild superficial damage in all six rats treated intravesically. Bladder wall destruction reached the muscular layer, with an abscess in one of six rats treated intravenously. After 3 weeks of PDT there was muscular necrosis with perforation and abscess from catheterization two of six rats treated intravesically and in three the bladder wall totally recovered. In the intravenous group the bladder walls were normal or had only mild superficial damage. Cytology of the urine sediment failed to detect half the tumours in the treatment groups. CONCLUSION: These results support the use of PDT with intravesical ALA-induced protoporphyrin X for treating superficial bladder carcinoma. Intravesical was better than intravenous ALA in eradicating bladder carcinoma with PDT.

Effect of the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor (PPAR) gamma2 gene on the expression of PPARgamma target genes in adipose tissue of massively obese subjects.

The aim was to study the effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) gamma2 gene on the expression of PPARgamma target genes in adipose tissue. Adipose tissue samples were collected from 30 massively obese subjects (10 men and 20 women) from omental, sc abdominal, and femoral depots. The mRNA expression of PPARgamma1, PPARgamma2, lipoprotein lipase, p85alpha phosphatidylinositol 3-kinase, and uncoupling protein 2 were quantified by reverse transcription-competitive PCR. The genotypes of Pro12Ala polymorphism were determined by single-strand conformation polymorphism analysis. The frequency of the Ala12 allele was 13.3% (8 Pro12Ala and 22 Pro12Pro). There were no differences in body weight, fat mass, and fasting serum leptin between the genotypes. The mRNA expression of p85alpha phosphatidylinositol 3-kinase was significantly lower in the omental fat of the Pro12Ala carriers than the Pro12Pro carriers (P < 0.01). It also appeared that PPARgamma2 expression was higher in men with Ala12 allele (P < 0.01). Interestingly, particularly in women, the expression of both PPARgamma splice variants was lower in omental than sc fat independently of the genotype (P < 0.05-0.01). The common Pro12Ala polymorphism of the PPARgamma2 gene has minor influence on mRNA expression of PPARgamma target genes in adipose tissue of obese subjects. Expression of both PPARgamma splice variants is dependent on fat depot: omental fat shows lower mRNA levels, compared with sc fat depots.

Reperfusion but not acute ischemia in pig small intestine induces transcriptionally mediated heat shock response in situ.

BACKGROUND: Although there is data on the cytoprotective role of heat shock proteins in intestinal ischemia-reperfusion, the effects of ischemia and reperfusion per se on the small intestinal heat shock response have been poorly characterized. METHODS: Four female pigs were subjected to 60-min ischemia by superior mesenteric artery occlusion followed by 360-min reperfusion. Systemic and local hemodynamics were monitored. Samples from the jejunal mucosa and muscularis were obtained for histology and for time series molecular biologic analyses of heat shock transcription factor 1 (HSF1), hsp70 mRNA and Hsp70 protein. RESULTS: A 30-min reperfusion of jejunum after a preceding 1-hour ischemia results in a significantly increased DNA-binding activity of HSF1, in a 10-fold increase of hsp70 mRNA in the mucosal and in a 7-fold increase in the muscular layers. Translational activation and accumulation of Hsp70 protein occurs after 60 min of reperfusion in the intestine. Nevertheless, a 60-min ischemia inducing mucosal detachment does not induce the heat shock response at any level analyzed. CONCLUSIONS: Ischemia alone is insufficient to induce the heat shock response, whereas subsequent reperfusion induces the response via transcriptionally mediated induction of Hsp70 synthesis both in the mucosal and muscular layers.

Preconditioning hyperthermia inhibits restitution of isolated Guinea pig gastric mucosa.

BACKGROUND: Superficial epithelial injury is followed by restitution which is based on the migration of the surviving mucosal cells to restore the disturbed epithelial continuity. There is previous data that heat-shock (HS) preconditioning may be utilized to enhance the tissue tolerance to injury. Yet, there is little data about the effect of preconditioning on restitution. METHODS: Guinea pig gastric mucosae were mounted and perfused in Ussing chambers. After stabilization, a HS (42 degrees C, 30 min) and concomitant heat-shock protein (Hsp) production was induced. After stabilization and reaching the normothermia, a superficial injury (1.25 mol/l NaCl) was induced. Subsequently, the tissue was allowed to restitute for 3 h. In some sets of experiments, protein synthesis was inhibited either with quercetin or with cycloheximide. During the experiment, transmucosal electrophysiological resistance (R) of the tissue was recorded. After the experiment, the mucosa was prepared for morphologic analysis and for Western blot. RESULTS: HS did not affect mucosal tolerance to hyperosmolar injury, but inhibited significantly restitution after injury and upregulated Hsp70 as well. The levels of Hsp70 correlated inversely with recovery of R and histology. Quercetin and cycloheximide abolished this effect of HS, while quercetin did not completely abolish Hsp70 upregulation. CONCLUSION: Hyperthermic preconditioning inhibits the restitution of gastrointestinal mucosa in correlation with Hsp70 levels. The inhibition of restitution is sensitive to blockades of de novo protein synthesis and of Hsp70 production.

Effect of alendronate on periprosthetic bone loss after total knee arthroplasty: a one-year, randomized, controlled trial of 19 patients.

Undesired bone loss around implants is considered to occur mainly because of a stress-shielding phenomenon. Bone surrounding the total knee arthroplasty (TKA) adjusts its mineral density and structure to meet new mechanical demands. Immobilization, in combination with local operative trauma to the bone and soft tissues, has an additional impact on bone loss. The clinical survival of TKA is associated with the quality and quantity of the surrounding bone environment. Poor bone quality and quantity may predispose to aseptic implant loosening and periprosthetic fractures. We investigated the efficacy of oral bisphosphonate (alendronate, Fosamax) with calcium (Calcichew) for the inhibition of early bone mineral density (BMD) loss after TKA in a prospective, randomized, one-year follow-up study. Periprosthetic BMD changes were measured with fan-beam dual-energy X-ray absorptiometry (DXA) in 19 patients with knee osteoarthrosis. Patients (n = 8) treated with 10 mg alendronate and 500 mg calcium daily maintained distal femoral BMD values close to the baseline values (P > 0.04), while patients receiving only 500 mg of calcium daily (n = 11) showed significant bone loss during the one-year follow-up (P < 0.015). The treatment groups differed significantly in metaphyseal anterior, posterior, diaphyseal, and metaphyseal total regions of interest (ROIs) (repeated measures ANOVA analyses, P = 0.019, P = 0.010, P = 0.022, and P = 0.024, respectively). Our results indicate that oral alendronate reduces early postoperative periprosthetic bone loss significantly. This therapeutic strategy may improve the results and longevity of primary total knee arthroplasties.

Relation of sex hormones to bone mineral density in middle-aged men during a 4 year exercise intervention trial.

Recent studies have emphasized the symbiotic role of estradiol and testosterone on bone metabolism. Several anthropomorphic-, lifestyle-, and dual-energy X-ray (DXA)-derived parameters were measured with respect to estradiol (E(2)), testosterone (T), free T (fT), and sex hormone-binding globulin (SHBG) in 140 men (aged 53-62 years) participating in a controlled, randomized exercise intervention trial. After 4 years of intervention, 132 (94.3%) men remained as participants. During the period of study, aerobic threshold increased significantly in the exercise intervention group compared with the reference group (13.4% vs. -1.9%: p < 0.023). Serum E(2) and fT were not convincingly related to bone mineral density (BMD) or BMD change. Aerobic threshold or the change in aerobic threshold were not associated with sex hormone or SHBG levels. Body mass index was a significant determinant of T (beta = -0.337), fT (beta = -0.293), and SHBG (beta = -0.306), and smoking predicted T (beta = 0.231) and fT (beta = 0.245). Alcohol intake was a significant determinant of E(2) (beta = 0.213). Ultimately there was no convincing relation between sex hormone levels and BMD or BMD change in middle-aged men.

Bone mineral density after the removal of intramedullary nails: a cross-sectional and longitudinal study.

We measured bone mineral density (BMD) using dual X-ray absorptiometry (DXA) at several sites in both fractured and nonfractured limbs in eight patients with femoral shaft fracture and six with tibial shaft fracture at the time of the intramedullary (IM) nail removal. Seven patients were followed up for an average of 13 months. The BMD at the proximal part of the femur and tibia was from 3% to 11% lower in the fractured side as compared to the nonfractured side. The greatest bone loss (13%-21%) was found in the operated distal tibia of the patients with tibial shaft fractures. At the fracture site of the femur, BMD was 10.5% ( P < 0.05) higher, possibly owing to fracture callus formation, whereas tibial shaft BMD was not increased. However, a calculated apparent volumetric BMDvol at the fracture site was 15%-16% decreased. Although BMDs of the fractured side almost reached the baseline level of the nonfractured side (96.9%-102.1%) by the final follow-up (>12 months), the absolute deficit was still 3%-9%. Surprisingly, significant BMD increases (5%-6%) were also detected in all proximal femoral measurement sites of the contralateral limb, which indirectly suggests that the uninjured limb may also suffer from bone loss after lower-extremity trauma. We conclude that clinically important bone loss exists in the proximal femur and proximal and distal tibia of the fractured limb at the time of IM nail removal. Although areal BMD was higher at the femoral fracture site, the lower apparent volumetric BMDvol suggests decreased mineralization and reduced strength of the fracture site. Although the present results do not suggest special recommendations for restricted weight bearing after the removal of IM nails, the relationship between decreased bone density and increased risk of fractures should be borne in mind.

Effects of fluid and dobutamine treatment on renal function during partial superior mesenteric artery occlusion and reperfusion.

OBJECTIVE: We compared the effects of dobutamine, fluid resuscitation and their combination on renal function during experimental intestinal ischaemia and reperfusion. MATERIALS AND METHODS: Superior mesenteric artery (SMA) blood flow was reduced to 30% from the baseline for 120 minutes in 24 anaesthetized pigs (ischaemic group); 24 pigs (sham group) served as non-ischaemic controls. The animals were further assigned into four treatment arms. In the control arms, the animals were given only basic fluid therapy. In the fluid therapy arms, pulmonary capillary wedge pressure (PCWP) was maintained at 10 mmHg with intravenous fluids. In the dobutamine treatment arm, dobutamine hydrochloride was infused at a dose of 10 microg/min/kg. In the combined dobutamine-fluid therapy arms, dobutamine at 10 microg/min/kg was given and PCWP was maintained at 10 mmHg with fluids. At 120 minutes, the occluder was released in all study groups and the animals were followed for an additional 60 minutes. Renal function was evaluated by means of serum and urine creatinine. urine volume and creatinine clearance. Systemic and regional haemodynamics as well as intramucosal pH, intramucosal-arterial pCO2 gradient, and portal venous-arterial lactate gradient were measured. RESULTS: In the ischaemic groups, diuresis increased and serum and urine creatinine decreased significantly in fluid (p < 0.01, p < 0.01 and p < 0.05, respectively) and dobutamine-fluid (p < 0.01, p < 0.001 and p < 0.001, respectively) treated groups during SMA ischaemia. After SMA reperfusion, diuresis decreased in control group (p < 0.05) and in animals treated with dobutamine alone (p < 0.01). In addition, urine creatinine increased in dobutamine treated group (p < 0.05), and creatinine clearance decreased in control group (p < 0.01). Renal function and diuresis during the SMA occlusion and reperfusion did not differ between ischaemic and sham groups. All fluid treated groups had lower serum creatinine during SMA occlusion than control groups (p < 0.001). CONCLUSIONS: Intestinal ischaemia caused by partial SMA occlusion did not influence renal function. On the contrary, SMA reperfusion resulted in a significant impairment of renal function both in ischaemic and sham operated animals. The impairment was most obvious in control groups and in animals treated with dobutamine alone.

Hormone sensitive lipase expression and adipose tissue metabolism show gender difference in obese subjects after weight loss.

OBJECTIVE: The effect of weight reduction on hormone sensitive lipase (HSL) and lipoprotein lipase (LPL) gene expression and their relationship with adipose tissue metabolism were studied in massively obese men and women. SUBJECTS: Seventeen obese subjects (eight men, nine women) participated in the study (age 44+/-2 y, weight 145+/-8 kg, fat 40+/-2% of body mass, mean+/-s.e.m.), who were going through a gastric-banding operation for weight reduction. MEASUREMENTS: HSL and LPL mRNA expressions were analyzed using the reverse transcription competitive polymerase chain reaction. Subcutaneous fat lipolysis was measured in vivo by microdialysis and in vitro in isolated subcutaneous abdominal adipocytes. Measurements were done before and after 1 y of weight reduction. RESULTS: Significant reductions in weight (for men -20.3+/-2.5%, for women -18.3+/-2.1% (mean+/-s.e.m.) and fat mass (for men -27.6+/-7.9%, for women -21.8+/-3.9%) were observed in both genders. In women HSL mRNA expression decreased by 31% (P=0.008) and LPL expression increased slightly, but nonsignificantly (42%, P=0.110). These changes were not observed in men. In men, inhibition of lipolysis with alpha(2)-adrenergic and adenosine agonist was improved (P=0.001) in isolated adipocytes. CONCLUSIONS: This study uncovers new differences between genders in adipocyte metabolism along with weight reduction. In women, the observed changes in HSL and LPL gene expression suggest that deposition of lipids into adipose tissue might be favored after weight reduction. In men, the results indicate improved responsiveness to inhibition in adipose tissue metabolism along with weight reduction.