Combining studies using effect sizes and quality scores: application to bone loss in postmenopausal women

This article presents a random effects model that uses effect sizes (ES) and quality scores to integrate results from investigations. An empirical example is given with data obtained from a meta-analysis on the effectiveness of physical activity in the prevention of bone loss in healthy postmenopausal women. A Medline search was performed to locate relevant studies published in French or English between January 1966 and May 1996. Three independent reviewers extracted data from studies. Effect sizes were calculated according to the method of Hedges and Olkin. A modified version of Chalmers' scale was utilized to calculate quality scores. DerSimonian and Laird's method with incorporation of the quality scores was used to estimate the overall effect size. Quality scores and the inverse of the variances were included as weights when combining studies. The overall estimate and standard error (SE) of the effect of physical activity on spinal bone mineral density loss in healthy postmenopausal women was ESoverall = 0.4263 (1.1361). When compared to other meta-analysis methods such as the fixed effects model and the model of DerSimonian and Laird without the quality score (DL), the new model generated comparable estimators (fixed effects model's ESoverall (SE) = 1.2724 (0.0139), DLs ESoverall (SE) = 0.3958 (1.2370)). Due to the heterogeneity that existed between studies, a random effects model was more appropriate then a fixed effects model. However, it resulted in wider confidence intervals, as expected. It was shown empirically that the model using quality scores generated narrower confidence intervals than the model of DL alone. The inclusion of covariates such as quality scores in meta-analyses permits the quantification of the variation between studies.     

Dietary caffeine intake and bone status of postmenopausal women

Dietary caffeine intake has been suggested as a risk factor for bone loss in postmenopausal women. We measured the bone density of both hips and the total body in 138 healthy, postmenopausal women aged 55-70 y who had either never used hormone replacement therapy (HRT) or had used HRT for < 1 y. In this cross-sectional study, participants were stratified according to their reported current and long-time caffeinated beverage use into one of three groups: low [0-2 cups (180 mL, or 6 oz per cup) caffeinated coffee per day], moderate (3-4 cups caffeinated coffee per day), or high (> or = 5 cups caffeinated coffee per day). Caffeine intake was measured from diet records and by gas chromatography of each subject's brewed, caffeinated beverages. No association between caffeine intake and any bone measurement was observed. The anthropometric and nutrient intakes of the three groups were similar. Compared with caffeine intake based on chemical analysis of brewed beverages, 3-d prospective food records and computer-assisted analysis overestimated caffeine intake by nearly two-thirds. In conclusion, the habitual dietary caffeine intake of this cohort of 138 postmenopausal women ranged from 0-1400 mg/d and was not associated with total body or hip bone mineral density measurements. This study does not support the notion that caffeine is a risk factor for bone loss in healthy postmenopausal women.     

Prevention of bone loss induced by thyroxine suppressive therapy in postmenopausal women: the effect of calcium and calcitonin

Although controversies exist on the possible adverse effect of T4 on bone mass, most studies reported bone loss in estrogen-deprived postmenopausal women taking suppressive doses of T4. We prospectively studied 46 postmenopausal women with carcinoma of thyroid for 2 yr to evaluate the rate of bone loss and assess whether calcium supplementation with or without intranasal calcitonin was able to decrease the rate of bone loss. All patients were receiving a stable dose of L-T4 (170 +/- 60 micrograms/day or 3.0 +/- 1.4 micrograms/kg.day) for more than 1 yr. All had TSH levels of 0.03 mIU/L or less and an elevated free T4 (FT4) index, but normal T3 levels. The calcium intake was low and averaged 507 +/- 384 g/day as assessed by dietary recall. The subjects were randomized into three groups: 1) intranasal calcitonin (200 IU daily) for 5 days/week plus 1000 mg calcium daily, 2) calcium alone, or 3) placebo. Total body and regional bone mineral density were measured by a dual energy x-ray absorptiometry bone densitometer at 6-month intervals. The results showed that both groups 1 and 2 had stable bone mass, whereas patients in groups 3 showed significant bone loss at the end of 2 yr (lumbar spine, 5.0%, hip, 6.7%, trochanter, 4.7%; Ward's triangle, 8.8%; P < 0.05), with bone mineral densities at all four regions lower than those in the other two groups (P < 0.05). There were no differences between groups 1 and 2. All three groups had elevated osteocalcin levels compared with age-matched reference controls. At 1 yr, the osteocalcin level decreased in groups 1 and 2, but remained significantly raised in group 3. No significant changes were detected in the bone-specific alkaline phosphatase levels. Urinary hydroxyproline excretion increased in group 3 at the end of 2 yr, but remained the same in groups 1 and 2. In conclusion, T4-suppressive therapy was associated with bone loss in postmenopausal women, which could be prevented by either calcium supplementation or intranasal calcitonin, although the latter did not provide additional benefit compared to calcium alone. However, careful titration of T4 dosage to maintain biochemical euthyroidism is a better way to avoid the adverse effect of T4 on bone.     

The influence of norethisterone acetate on urinary urodilatin excretion in postmenopausal women

Malignant hyperthermia developed in two Landrace x Large White pigs, 75 and 105 minutes after the induction of anaesthesia with halothane. Rapid treatment and discontinuation of halothane anaesthesia were unable to reverse the condition in the first case but were successful in the second. The delayed onset of malignant hyperthermia after delivery of halothane is unusual and for successful treatment careful monitoring and rapid and aggressive therapy are needed.     

T score of trabecular and cortical bone in normal postmenopausal women

CD4+ T cells may be assigned a functional status (Th1 or Th2) according to the cytokines they produce including IL-2, IFN-gamma and IL-4. Th1 and Th2 CD4+ T cells deliver different isotype-switching signals to antigen-specific B cells which bias the serum Ig isotypes. The stimulation of Th1 or Th2 responses is influenced by adjuvants and administration of antigen in IFA results in Th1 unresponsiveness as evidenced by: (i) reduced T cell proliferation to antigen; (ii) reduced IFN-gamma production in response to antigen; and (iii) reduced IgG2a isotype antigen-specific antibodies following antigen/CFA challenge. The impact of established human gamma globulin (HGG) specific Th1 unresponsiveness on subsequent immunization with an unrelated antigen, human serum albumin (HSA) in Th1-inducing CFA was then examined. When subsequently challenged with a mixture of HSA and HGG in CFA the HGG-specific Th1 unresponsiveness was infectious and dominant, preventing the induction of a Th1 response to HSA. Reduced T cell proliferation, IFN-gamma production and IgG2a antibody were consequently observed in response to HSA. The HGG-specific Th1 unresponsiveness was not infectious when HGG/CFA and HSA/CFA were administered at separate sites. This demonstrates that antigen-specific Th1 unresponsiveness can be infectious for new, molecularly unrelated antigens and supports studies showing that Th1-mediated autoimmune diseases such as experimental allergic encephalomyelitis (EAE) and diabetes can be ameliorated using antigens molecularly distinct from the disease-inducing immunogen.     

Regional bone mineral density interrelationships in normal and osteoporotic postmenopausal women

We describe a prospective study in which bone mineral density (BMD) was measured in total body and regions, proximal femur, lumbar spine, and forearm in 84 apparently normal postmenopausal women with normal spinal radiographs and in 47 women with 1-10 wedged or compressed vertebrae. There was a history of peripheral fracture in 35 of the 84 controls and 30 of the 47 osteoporotics (p < 0.02) but there was no association between vertebral fracture and wrist fracture. At all sites and regions, the differences in BMD between the "normal"and "osteoporotic" women was highly significant and all but "ribs" and "arms" remained significant after correction for menopausal age. In the whole set, and in both subgroups, the coefficients of correlation between sites and regions were all highly significant (p < 0.001). Nonetheless, some sites discriminated better between the two groups than others. Standardized odds ratios (OR) for vertebral fracture versus no-fracture were calculated by logistic regression and expressed as the rise in OR for each standard deviation (SD) fall in bone density. This ratio was greatest (3.4) in "pelvis" and weakest (1.7) in "ribs" but all were statistically significant. Geometric mean regression equations were calculated for all the 78 possible pairs of sites and regions in the 84 normal subjects and the deviations of the osteoporotic women from these normal slopes calculated. In most pairs of sites and regions, the vertebral fracture cases were scattered around the normal group's slope but fell lower down on both axes. The bone deficits in the osteoporotics compared with young normal women ranged from -14% in "head" to -40% in Ward's triangle and the T-scores ranged from -1.9 in "ribs" to -3.9 in the forearm. Sensitivity ranged from 17% in "ribs" to 36.2% in Ward's triangle. Specificity varied between 88 and 94% and the percent correctly classified ranged from 62.6% in "ribs" to 72.5% in Ward's triangle. We conclude that primary postmenopausal osteoporosis affects the entire skeleton but that some sites discriminate better between vertebral fracture and nonfracture cases regardless of whether they represent cortical or trabecular bone.     

Vitamin D receptor gene polymorphism is associated with urinary calcium excretion but not with bone mineral density in postmenopausal women

Polymorphism of vitamin D receptor (VDR) gene has been found to be associated with serum osteocalcin (OC) levels and bone mineral density (BMD) in Caucasian identical twins and unrelated postmenopausal women. Being ethnically different and living in a geographic area with adequate vitamin D status due to abundant sunshine exposure, it is unclear whether VDR gene polymorphism will affect bone mass in Thai population. In the present study, we investigated the association between VDR gene polymorphism and bone metabolism in Thai postmenopausal women. Subjects consisted of 84 postmenopausal women. Bsm I, Taq I and Apa I polymorphisms of VDR gene were determined by PCR-RFLP. B, T and A represent the absence of the corresponding restriction sites while b, t and a indicate the presence of the restriction sites. Data were expressed as mean +/- SE. Sixty-six subjects (78.6%) had bb genotype while 18 (21.4%) had Bb genotype. None of the subjects was found to have BB genotype. Taq I restriction site was in linkage disequilibrium to the Bsm I site. For Apa I polymorphism, 33 (39.3%), 42 (50.0%) and 9 (10.7%) of the subjects had aa, Aa and AA genotypes, respectively. There was no significant difference in serum intact OC levels and BMD at various skeletal sites among subjects with different genotypes. Despite the lack of difference in BMD and intact OC levels, subjects with bb genotype had higher 24-hour urinary calcium excretion than those with Bb genotype (bb, 6.1 +/- 0.3 mmol/day; Bb, 4.4 +/- 0.6 mmol/day; p < 0.05). The effect of Bsm I VDR genotype was still significant (p < 0.05) after dietary calcium intake was controlled using analysis of covariance. Despite the difference in urinary calcium levels, there was no significant difference in fractional excretion of calcium among subjects with different Bsm I-related genotypes, suggesting that the effect of the VDR gene polymorphism on urinary calcium excretion is more likely due to the effect on intestinal calcium absorption rather than renal tubular calcium reabsorption. We conclude that VDR genotype distributions in Thai postmenopausal women are different from those reported in Caucasians. VDR gene polymorphism does not appear to be associated with BMD or bone turnover in Thai postmenopausal women. However, Bsm I VDR polymorphism may have physiologic role in calcium homeostatasis by modulating intestinal calcium absorption.     

Effects of cyclical etidronate therapy on bone loss in early postmenopausal women who are not undergoing hormonal replacement therapy

1. Pacing-induced heart failure was studied in eight dogs. Heart failure was induced by right ventricular pacing at 250-260 beats/min for 6 weeks. Evidence of heart failure was determined clinically and by measurement of left ventricular (LV) dimensions by transoesophageal echocardiography. 2. Haemodynamic measurements of LV pressure, maximum rate of rise of LV pressure (LVdP/dtmax), cardiac output, mean arterial pressure, heart rate, pulmonary artery and pulmonary wedge pressures were made during infusion of solvent (control) and the calcium sensitizer EMD 57033 (0.6 mg min-1 kg-1). 3. The degree of heart failure varied from mild to severe in different individuals, but in each case EMD 57033 exerted a positive inotropic effect on LV haemodynamics and dimension. 4. The positive inotropic effect of the calcium sensitizer was manifest by increased peak LVdP/dt with a subsequent increase in cardiac output at the same mean arterial pressure. 5. This study clearly demonstrates that there is the potential for improvement of contractility of the failing myocardium of the intact mammal by an agent with a mechanism of action which does not involve an increase in intracellular calcium.     

Effects of alendronate on bone turnover markers in early postmenopausal women

BACKGROUND: Alendronate sodium (Fosamax, Merck, Sharp & Dohme, Whitehouse Station, NJ, USA) is an aminobisphosphonate that can inhibit osteoclast-mediated bone resorption activity to reduce bone turnover rate and improve progressive gains in bone mass. METHODS: This was a randomized, double-blind, placebo-controlled study comparing the effects on bone turnover markers between daily treatment with alendronate sodium 10 mg and placebo. Forty early postmenopausal women completed three months of treatment. The bone turnover rate was determined by measuring the biochemical markers at baseline, week 6 and at the end of the three-month treatment period. All adverse events were recorded during each follow-up visit. RESULTS: Patients receiving alendronate treatment had a significant decrease in urinary excretion of the bone resorption marker deoxypyridinoline (Dpd) as well as one of the bone formation markers, bone-specific alkaline phosphatase (AlkP-B). Patients receiving placebo tended to have increased urinary excretion of bone resorption and formation markers. At the end of three months, the mean percentage change of Dpd and AlkP-B from baseline in the group receiving 10 mg alendronate was 30.49% and 29.45% reduction, respectively. The placebo group had 2.39% and 1.52% increase, respectively. Overall, three biochemical markers (Dpd, AlkP-B and osteocalcin) differed significantly between the treatment and control groups after three months of treatment. The drug was well tolerated, without a significant increase in incidence of adverse effects such as gastrointestinal discomfort and esophageal irritation. CONCLUSIONS: Bone turnover rate decreased quickly following drug administration. The incidence of adverse effects did not differ significantly between the alendronate and placebo groups. Alendronate is, therefore, recommended as an effective nonhormonal treatment for postmenopausal osteoporosis.     

Body weight and bone mineral density in postmenopausal women with primary hyperparathyroidism

OBJECTIVE: To assess bone mineral density and body composition in postmenopausal women with primary hyperparathyroidism. DESIGN: Cross-sectional study with an age-matched control group. SETTING: University teaching hospital. PATIENTS: 41 postmenopausal women with mild primary hyperparathyroidism and 43 eucalcemic, age-matched controls. MEASUREMENTS: Total body, lumbar spine, and proximal femoral (femoral neck, Ward's triangle, and trochanter) bone mineral density; body composition; and fat distribution were measured using dual-energy x-ray absorptiometry. RESULTS: Women with primary hyperparathyroidism were heavier (75.5 kg compared with 66.3 kg; difference, 9.2 kg [95% CI, 3.7 to 14.7 kg]; P = 0.002), had a higher fat mass (33.3 kg compared with 26.1 kg; difference, 7.2 kg [CI, 3.0 to 11.4 kg]; P = 0.001), and had a more android pattern of fat distribution (android-to-gynoid fat ratio, 1.05 compared with 0.84; difference, 0.21 [CI, 0.1 to 0.32]; P = 0.0004) than the controls. Unadjusted bone mineral density was similar in patients and controls at all sites: total body, 0.990 compared with 1.023 g/cm2 (difference, 0.033; CI, -0.004 to 0.070); posteroanterior lumbar spine, 1.032 compared with 1.018 g/cm2 (difference, 0.014; CI, -0.031 to 0.059); lateral lumbar spine, 0.569 compared with 0.528 g/cm2 (difference, 0.041; CI, -0.022 to 0.104); femoral neck, 0.799 compared with 0.825 g/cm2 (difference, 0.026; CI, -0.072 to 0.124); Ward's triangle, 0.653 compared with 0.677 g/cm2 (difference, 0.024; CI, -0.035 to 0.089); trochanter, 0.734 compared with 0.733 g/cm2 (difference, 0.001; CI, -0.024 to 0.026); and arms, 0.720 compared with 0.739 g/cm2 (difference, 0.019; CI, -0.015 to 0.053). After adjustment for body weight, bone mineral density in women with primary hyperparathyroidism was lower than that in controls for total body (P = 0.0004), femoral neck (P = 0.001), Ward's triangle (P = 0.01), trochanter (P = 0.02), and arms (P = 0.0006). Spinal bone mineral density did not differ between groups. CONCLUSIONS: Body weight, total body fat mass, and proportion of android fat are increased in postmenopausal women with primary hyperparathyroidism; these unexplained factors may be relevant to the increased incidence of cardiovascular disease in this condition. Unadjusted bone mineral density values are similar in patients with primary hyperparathyroidism and in controls, suggesting that this condition is not associated with an increased risk for fracture.     

Bone loss associated with a high fibre weight reduction diet in postmenopausal women

OBJECTIVE: To examine the effect of high fibre weight reduction on bone density in postmenopausal women. DESIGN: Case-control study. SETTING: Hospital outpatient dietetic clinic and Osteoporosis Screening Unit. SUBJECTS AND INTERVENTIONS: Sixteen overweight volunteers who followed a high fibre reducing diet for 6 months, to lose 20% of excess body weight (above body mass index 25 kg/m2), and returned to their starting weight by the end of a further 6 months. Forty-six non-dieting controls, matched for age and years postmenopause, selected from screening unit volunteer register. RESULTS: Annual percentage changes in lumbar spine bone mineral density, measured by dual energy X-ray absorptiometry were: controls -2.5% (SE 0.5), dieters -4.8% (0.9), 95% confidence interval of difference between groups -0.2 to -4.3% (P = 0.03); femoral neck bone density controls -2.5% (0.5), dieters -2.1% (0.9), 95% confidence interval of difference -1.7 to 2.5% (P = 0.69). CONCLUSIONS: High fibre weight reduction in postmenopausal women significantly increased annual bone loss from the lumbar spine. This loss was not reversed by weight regain in the second 6 months. Repeated cycles of high fibre weight loss and weight gain may increase the risk of spinal osteoporosis.     

Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass

Genetic mosaic maize plants that contained dwarf1 sectors in otherwise normal plants were analyzed. The analysis of dwarf1 sector growth relative to the surrounding wild-type tissue should test the hypothesis that Dwarf1 controls the production of a diffusible factor. Maize dwarf1 sectors did not show altered growth relative to the surrounding tissue, indicating that Dwarf1 controls the production of a diffusible factor. As Dwarf1 has been proposed to control the conversion of GA20 to biologically active GA1, these results suggest that GA, itself is the diffusible factor.     

Evidence that increased calcium intake does not prevent early postmenopausal bone loss

Calcium's ability to prevent bone loss in early postmenopausal women is controversial. We used data on 394 women from the placebo group of the Early Postmenopausal Interventional Cohort study, a clinical trial of alendronate, to investigate the relation of calcium intake to bone loss. Calcium intake was recorded, and bone mineral density (BMD) (in the lumbar spine, total body, forearm, and hip) and biochemical markers of bone turnover (serum total alkaline phosphatase, serum osteocalcin, and urinary N-telopeptide crosslink levels) were measured at baseline and annually thereafter. Women whose baseline calcium intake was <500 mg/d were advised to increase their calcium intake. Mean (+/- SE) BMD decreased by 1.9% +/- 0.16% at the lumbar spine and 1.6% +/- 0.14% at the hip over the 24-month period. Despite wide variations in baseline calcium intake and changes in calcium intake, these measures were not significantly associated with changes in BMD or bone turnover. Even women whose total calcium intake was >1333 mg/d (the highest tertile of total calcium intake) showed a decline in BMD of almost 2%, similar to declines in the lower two tertiles of total calcium intake (<869 and 869-1333 mg/d, respectively). Increased calcium intake resulted in modest mean increases of approximately 200 mg/d. We were unable to demonstrate that increases of this magnitude or much greater (1 g/d) were protective against declines in BMD at any site, even in women who had the lowest calcium intake at baseline. In addition to adequate calcium intake, more effective therapy appears to be required when the therapeutic goal is to increase or maintain BMD.     

Determinants of radial bone density as measured by PQCT in pre- and postmenopausal women: the role of bone size

OBJECTIVE: To investigate characteristics of children and adolescents with a history of combined pharmacotherapy (CPT) and compare them with a group with no history of CPT. METHOD: Eighty-three consecutive admissions to a residential treatment center were divided into a CPT and a no-CPT group based on treatment history and compared by chart review. Prevalence of lifetime psychiatric medication use and CPT exposure were assessed. Demographic, diagnostic, treatment, behavioral, and medication variables were compared across the two groups. RESULTS: Medication use was present in the treatment history for 89.2% and a history of CPT was found for 60.3% of subjects. Admission to current placement from inpatient psychiatry, lifetime number of psychiatric placements, lifetime number of psychiatric diagnoses, and nonseizure neuropsychiatric comorbidity were significantly associated with CPT. Aggression and neuroleptic use were also significantly associated with CPT. Admission psychiatric diagnostic comorbidity was not associated with CPT. CONCLUSIONS: A high prevalence of psychiatric medication use and CPT was found in this population. Variables assessing illness severity, aggressive behavior, and nonseizure neuropsychiatric comorbidity may identify youths in psychiatric treatment settings with a high prevalence of past or current CPT exposure. Further research on the CPT of aggression is warranted.     

Bowel dysfunction in postmenopausal women

BACKGROUND/AIMS: The perimenopausal and postmenopausal states are frequently accompanied by a variety of symptoms of hormonal imbalance. Although vasomotor, vaginal and genitourinary symptoms prevail, gastrointestinal complaints such as abdominal bloating may occur. In this study, we investigated the nature and prevalence of gastrointestinal and irritable bowel syndrome (IBS)-type complaints in women going through their climacteric and postmenopausal periods. PATIENTS/METHODS: 228 women (170 postmenopausal and 58 premenopausal) who presented for evaluation at a primary care practice limited to women's health were evaluated prospectively by a previously validated gastrointestinal symptoms questionnaire designed to evaluate symptoms suggestive of IBS. At the time of their participation in the study, none of these women was presenting for evaluation of abdominal or genitourinary symptoms. RESULTS: Thirty-eight percent of postmenopausal women reported altered bowel function, in contrast to 14% of premenopausal ones (p < 0.001). Despite this, the two groups did not differ in regards to the occurrence of abdominal pain, diarrhea or constipation, suggestive of IBS. The prevalence of IBS-type complaints peaked to 36% during the climacteric period (40-49 years). Laxative usage (9.4% prevalence), gaseousness/excessive flatulence (48% prevalence) and heart-burn/acid regurgitation (34% prevalence) were also more common among postmenopausal women. Estrogen use did not affect gastrointestinal symptoms in any of the two groups. CONCLUSIONS: Although the possible role of aging on symptom perception-regardless of hormonal status-cannot be ruled out, these results suggest that peri- and postmenopausal women have a high prevalence of altered bowel function and IBS-like gastrointestinal complaints that should be carefully assessed. If the diagnosis of IBS is confirmed, appropriate treatment may improve patients' symptoms, although this approach requires further study.     

Use of androgens in postmenopausal women

Immunohistochemical study of the distribution of glutamate receptor subunits 1-4 (GluR1-4), NMDA receptor subunit 1 and metabotropic glutamate receptor subtypes 1-3 (mGluR1-3) in the ependymal cells of the caudal medulla oblongata and upper thoracic spinal cord was carried out. The results showed that ependymal cells and tanycytes expressed only the metabotropic receptor subtype, mGluR1 alpha. Some of the mGluR1 alpha-positive long basal processes of the tanycytes reached the pia mater; some made contact with capillaries. It was suggested that the activity of the these mGluR 1 a-positive tanycytes may be regulated by the CSF and blood. The presence of many mGluR1 alpha positive fibres in the area postrema suggests that mGluR1 alpha subtype in this region may be involved in cardiovascular regulation.     

Plasma leptin values in relation to bone mass and density and to dynamic biochemical markers of bone resorption and formation in postmenopausal women

A case of measles in a 26-year-old Japanese man is reported. A skin specimen taken on the third eruptive day from a maculopapular eruption on his chest was immunohistopathologically and electron microscopically examined using a rabbit polyclonal antibody against the nucleocapsid protein of the measles virus. The measles virus antigen was found in the inner cells of the acrosyringium and hair follicles. The measles virus nucleocapsid was electron microscopically identified in the nuclei of the inner cells of the acrosyringium. The findings suggest that the sweat from skin lesions might contain the measles virus.     

Evaluation of optimal measuring site and index by QDR4500A for postmenopausal bone loss]

Adjuvant therapy and microsurgery have allowed advances in surgical extirpation of lower extremity neoplasms. This retrospective study was designed to evaluate the microvascular transfer for lower extremity reconstruction in patients receiving pre- or post-operative irradiation and chemotherapy alone and in combination. Over a 5-year period, 24 free tissue transfers were performed in 22 patients undergoing surgical resection with adjuvant therapy for lower extremity neoplasms. There were 13 male and 9 female patients with an average age of 51 years. The latissimus dorsi muscle was most commonly transferred (N = 15). Eighteen tumors received pre- and three received postoperative radiotherapy. Two tumors received a combination of radiotherapy and brachytherapy. Pre- and/or postoperative chemotherapy was used in 14 patients. Twelve of these patients had both chemo- and radiation therapy. A total of six complications occurred, with no flap loss. Complications were evenly distributed among adjuvant regimens. All patients who underwent attempted limb salvage were able to ambulate postoperatively, except for 1 patients who had local recurrence. In conclusion, adjuvant therapy did not increase the complication rate for free tissue transfer in the lower extremity. Adjuvant therapy did not require alterations in the free tissue transfer and, similarly, free tissue transfer did not alter adjuvant therapy. We believe that free tissue transfer in complicated wounds allows for better wound healing with adjuvant therapy rather than local or primary wound closure alone.