Imaging of diabetic foot infections.

Complications from diabetic foot infections are a leading cause of nontraumatic lower-extremity amputations. Nearly 85% of these amputations result from an infected foot ulcer. Osteomyelitis is present in approximately 20% of diabetic foot infections. It is imperative that clinicians make quick and successful diagnoses of diabetic foot osteomyelitis (DFO) because a delay in treatment may lead to worsening outcomes. Imaging studies, such as plain films, bone scans, musculoskeletal ultrasound, computerized tomography scans, magnetic resonance imaging, and positron emission tomography scans, aid in the diagnosis. However, there are several mimickers of DFO, which present problems to making a correct diagnosis.

Zoledronic acid versus alendronate for the prevention of bone loss after heart or liver transplantation.

CONTEXT: The first year after transplantation is characterized by rapid bone loss. OBJECTIVE: The aim of this study was to compare zoledronic acid (zoledronate) and alendronate for prevention of transplantation bone loss. DESIGN AND SETTING: A randomized clinical trial was conducted at a transplantation center. PATIENTS: The study included 84 adults undergoing heart or liver transplantation and a concurrently transplanted, nonrandomized reference group of 27 adults with T scores greater than -1.5. INTERVENTIONS: Alendronate (70 mg weekly for 12 months) or one 5-mg infusion of zoledronate were both initiated 26 ± 8 d after transplantation. MAIN OUTCOME MEASURES: The primary outcome was total hip bone mineral density (BMD) 1 yr after transplantation. Secondary outcomes included femoral neck and lumbar spine BMD and serum C-telopeptide, a bone resorption marker. RESULTS: In the reference group, BMD declined at the spine and hip (P < 0.001). In the randomized groups, hip BMD remained stable. Spine BMD increased in the zoledronate group and did not change in the alendronate group; at 12 months, the 2.2% difference between groups (95% confidence interval, 0.6 to 3.9%; P = 0.009) favored zoledronate. In heart transplant patients, spine BMD declined in the alendronate and increased in the zoledronate group (-3.0 vs. +1.6%, respectively; between-group difference, 4.2%; 95% confidence interval, 2.1 to 6.3%; P < 0.001). In liver transplant patients, spine BMD increased comparably in both groups. Twelve-month C-telopeptide was lower in the zoledronate group than in the alendronate group (79 vs. 49%; P = 0.04). CONCLUSIONS: One 5-mg infusion of zoledronate and weekly alendronate prevent bone loss at the hip and, in liver transplant patients, increase spine BMD. In heart transplant patients, spine bone BMD remained stable with zoledronate but decreased with alendronate.

Abnormal bone microarchitecture and evidence of osteoblast dysfunction in premenopausal women with idiopathic osteoporosis.

CONTEXT: Idiopathic osteoporosis (IOP) in premenopausal women is an uncommon disorder of uncertain pathogenesis in which fragility fractures occur in otherwise healthy women with intact gonadal function. It is unclear whether women with idiopathic low bone mineral density and no history of fragility fractures have osteoporosis. OBJECTIVE: The objective of the study was to elucidate the microarchitectural and remodeling features of premenopausal women with IOP. DESIGN: We performed transiliac biopsies after tetracycline labeling in 104 women: 45 with fragility fractures (IOP), 19 with idiopathic low bone mineral density (Z score ≤-2.0) and 40 controls. Biopsies were analyzed by two-dimensional quantitative histomorphometry and three-dimensional microcomputed tomography. Bone stiffness was estimated using finite element analysis. RESULTS: Compared with controls, affected women had thinner cortices; fewer, thinner, more widely separated, and heterogeneously distributed trabeculae; reduced stiffness; and lower osteoid width and mean wall width. All parameters were indistinguishable between women with IOP and idiopathic low bone mineral density. Although there were no group differences in dynamic histomorphometric remodeling parameters, serum calciotropic hormones, bone turnover markers, or IGF-I, subjects in the lowest tertile of bone formation rate had significantly lower osteoid and wall width, more severely disrupted microarchitecture, lower stiffness, and higher serum IGF-I than those in the upper two tertiles, suggesting that women with low turnover IOP have osteoblast dysfunction with resistance to IGF-I. Subjects with high bone turnover had significantly higher serum 1,25 dihydroxyvitamin D levels and a nonsignificant trend toward higher serum PTH and urinary calcium excretion. CONCLUSIONS: These results suggest that the diagnosis of IOP should not require a history of fracture. Women with IOP may have high, normal or low bone turnover; those with low bone turnover have the most marked deficits in microarchitecture and stiffness. These results also suggest that the pathogenesis of idiopathic osteoporosis is heterogeneous and may differ according to remodeling activity.

Discriminants of prevalent fractures in chronic kidney disease.

Patients with chronic kidney disease (CKD) have higher rates of fracture than the general population. Increased bone remodeling, leading to microarchitectural deterioration and increased fragility, may accompany declining kidney function, but there are no reliable methods to identify patients at increased risk for fracture. In this cross-sectional study of 82 patients with predialysis CKD, high-resolution imaging revealed that the 23 patients with current fractures had significantly lower areal density at the femoral neck; total, cortical, and trabecular volumetric bone density; cortical area and thickness; and trabecular thickness. Compared with levels in the lowest tertile, higher levels of osteocalcin, procollagen type-1 N-terminal propeptide, and tartrate-resistant acid phosphatase 5b were associated with higher odds of fracture, even after adjustment for femoral neck T-score. Discrimination of fracture prevalence was best with a femoral neck T-score of -2.0 or less and a value in the upper two tertiles for osteocalcin, procollagen type-1 N-terminal propeptide, or tartrate-resistant acid phosphatase 5b; these values corresponded to the upper half of the normal premenopausal reference range. In summary, these cross-sectional data suggest that measurement of bone turnover markers may increase the diagnostic accuracy of densitometry to identify patients with CKD at high risk for fracture.

Incidence of immediate gadolinium contrast media reactions.

OBJECTIVE: Our objective was to determine the incidence of immediate adverse events for gadolinium-based contrast agents. MATERIALS AND METHODS: All gadolinium-based contrast agent adverse events reported to radiology quality assurance committees were graded according to American College of Radiology criteria and divided by the total number of injections to determine incidence during the past 10 years. For each event, an age- and examination-matched control patient was identified to compare sex, weight, creatinine, eosinophil count, allergic history and gadolinium-based contrast agent dose differences. The U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database was analyzed to compare local experience to national trends. RESULTS: Abdominal MRI had the highest rates of adverse events, 0.013% compared with brain (0.0045%, p < 0.001) or spine (0.0034%, p < 0.001). Adverse events were more likely in women, with a female to male ratio of 3.3, and in patients with history of prior allergic reactions (p < 0.001). Immediate adverse events rates were 0.2, 0.5, 1.2, and 3.3 per 1,000 injections for gadodiamide, gadopentetate dimeglumine, gadobenate dimeglumine, and gadoteridol, respectively. Gadobenate dimeglumine had more severe patient reactions, including three patients who arrested (defined as the patient becoming unresponsive and the code team being called), one of whom died. From 2004 to 2009, the FDA received reports on 40 gadolinium-based contrast agent U.S. deaths unrelated to nephrogenic systemic fibrosis, with an incidence per million doses of 0.15, 0.19, 0.97, 2.7, and 0.7 for gadodiamide, gadoversetimide, gadopentetate dimeglumine, gadobenate dimeglumine, and gadoteridol, respectively. CONCLUSION: This limited retrospective analysis shows that gadolinium-based contrast agents are very safe, with only rare reports of death, and raises the possibility that nonionic linear gadolinium-based contrast agents and gadopentetate dimeglumine may have fewer severe immediate adverse events compared with gadobenate dimeglumine.

Bone mass and microarchitecture in CKD patients with fracture.

Patients with predialysis chronic kidney disease (CKD) have increased risk for fracture, but the structural mechanisms underlying this increased skeletal fragility are unknown. We measured areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry at the spine, hip, and radius, and we measured volumetric BMD (vBMD), geometry, and microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT) at the radius and tibia in patients with CKD: 32 with fracture and 59 without fracture. Patients with fracture had lower aBMD at the spine, total hip, femoral neck, and the ultradistal radius, the last having the strongest association with fracture. By HR-pQCT of the radius, patients with fracture had lower cortical area and thickness, total and trabecular vBMD, and trabecular number and greater trabecular separation and network heterogeneity. At the tibia, patients with fracture had significantly lower cortical area, thickness, and total and cortical density. Total vBMD at both radius and tibia most strongly associated with fracture. By receiver operator characteristic curve analysis, patients with longer duration of CKD had area under the curve of >0.75 for aBMD at both hip sites and the ultradistal radius, vBMD and geometry at the radius and tibia, and microarchitecture at the tibia. In summary, patients with predialysis CKD and fractures have lower aBMD by dual-energy x-ray absorptiometry and lower vBMD, thinner cortices, and trabecular loss by HR-pQCT. These density and structural differences may underlie the increased susceptibility to fracture among patients with CKD.

Discontinuing antiresorptive therapy one year after cardiac transplantation: effect on bone density and bone turnover.

BACKGROUND: We have previously reported that subjects randomized to alendronate or calcitriol immediately after cardiac transplantation sustained minimal bone loss during the first year, significantly less than a concurrently transplanted reference group that received calcium and parent vitamin D. In this extension, we evaluated the effect of discontinuing alendronate or calcitriol on bone loss and biochemical markers of bone turnover during the second year. We hypothesized that subjects who discontinued alendronate, which has a long half-life in bone, would not sustain significant bone loss. As the half-life of calcitriol is short, we hypothesized that there would be significant bone loss after discontinuing calcitriol. METHODS: We measured bone density (BMD), calciotropic hormones and bone turnover markers at 12, 18, and 24 months after transplantation in adherent subjects who completed the randomized trial on alendronate or calcitriol, and in reference subjects who had received no preventive therapy. RESULTS: In all, 75 subjects (34 alendronate, 25 calcitriol, 16 reference) participated. During the second year, the bone resorption marker, serum N-telopeptide, rose by 27% in the calcitriol group (P< or =0.001). Bone alkaline phosphatase, a bone formation marker, increased by 54% in the calcitriol group (P< or =0.001) and by 32% in the alendronate group (P< or =0.001). BMD did not change significantly at any site in either randomized group. CONCLUSIONS: After discontinuing alendronate or calcitriol, BMD remained stable during the second year after cardiac transplantation, despite a significant increase in a biochemical marker of bone resorption in the calcitriol group. This suggests that antiresorptive therapy may be discontinued at the end of the first posttransplantation year in cardiac transplant recipients without resumption of rapid bone loss. However, as increased bone turnover may predict future bone loss and fractures, such patients warrant observation to ensure that BMD remains stable long-term.

Osteoporosis in adult survivors of adolescent cardiac transplantation may be related to hyperparathyroidism, mild renal insufficiency, and increased bone turnover.

BACKGROUND: Osteoporosis is common in adults who undergo cardiac transplantation. We hypothesized that adolescent cardiac transplant recipients also develop osteoporosis, which would persist into adulthood. METHODS: We evaluated 9 adult survivors of adolescent cardiac transplantation, aged 21-32, in a cross-sectional, case-control study comparing bone mineral density, indices of mineral metabolism, and bone turnover markers. RESULTS: Osteoporosis (Z score < or = -2.0) was present in 56% of transplant recipients at the lumbar spine, 33% at the femoral neck, and 100% at the one-third radius. Subjects had mean bone mineral density Z scores of -2.3 +/- 0.9 at the spine, -1.6 +/- 0.7 at the femoral neck, and -3.2 +/- 0.7 at the one-third radius, significantly lower than controls at all sites (p < 0.001). Serum creatinine and vitamin D metabolites were normal and did not differ between subjects and controls. Serum calcium was lower, blood urea nitrogen was elevated, and creatinine clearance tended to be lower in transplant recipients. Parathyroid hormone (PTH) levels were 3-fold higher in subjects than controls, and 75% of subjects had elevated PTH levels. Markers of bone turnover were significantly higher in subjects than controls. CONCLUSIONS: Adult survivors of adolescent cardiac transplantation have mild renal insufficiency, secondary hyperparathyroidism, and biochemical evidence of increased bone turnover. Osteoporosis is common in these patients, particularly at the one-third radius, a site sensitive to the catabolic effects of sustained excessive PTH secretion. We conclude that adult survivors of adolescent cardiac transplantation should be evaluated for hyperparathyroidism and osteoporosis.

MRI of seemingly isolated greater trochanteric fractures.

OBJECTIVE: The objective of this article is to show that greater trochanteric fractures commonly perceived on routine radiographs as isolated are often neither isolated nor minor and that MR images can serve as a basis for more informed treatment by revealing the actual extent of such fractures in acute posttraumatic settings. CONCLUSION: A pitfall in diagnosing seemingly isolated greater trochanteric fractures on routinely used imaging techniques lies in the fact that the injuries usually involve a large anatomic area. In our experience, MRI more accurately defines the true geographic extent of greater trochanteric fractures sustained through acute trauma than do radiography and bone scintigraphy and thus could provide a more reliable basis for anticipating complications and for planning appropriate treatment.

Alendronate versus calcitriol for the prevention of bone loss after cardiac transplantation.

BACKGROUND: Osteoporosis is a well-known complication of cardiac transplantation. We conducted a randomized trial comparing alendronate with calcitriol for the prevention of bone loss during the first year after cardiac transplantation. METHODS: A total of 149 patients were randomly assigned to receive either alendronate (10 mg per day) or calcitriol (0.5 microg per day) a mean (+/-SD) of 21+/-11 days after transplantation. Estimates of bone loss and the incidence of fractures among untreated patients were obtained from a reference group of 27 prospectively recruited patients who received cardiac transplants within the same period as the intervention groups. RESULTS: At one year, the bone mineral density at the lumbar spine had decreased by a mean of 0.7 percent in the alendronate group and 1.6 percent in the calcitriol group (P=0.25 for the test of no difference). The bone mineral density at the femoral neck decreased by a mean of 1.7 percent in the alendronate group and 2.1 percent in the calcitriol group (P=0.69). In the reference group, the mean bone mineral density at the lumbar spine decreased by 3.2 percent (P=0.03 for the comparison with the alendronate group; P=0.15 for the comparison with the calcitriol group), and the mean density at the femoral neck decreased by 6.2 percent (P=0.001 for comparisons with both intervention groups). The incidence of vertebral fractures did not differ significantly among the groups (6.8 percent in the alendronate group, 3.6 percent in the calcitriol group, and 13.6 percent in the reference group). Hypercalciuria developed in 27 percent of the patients in the calcitriol group and 7 percent of those in the alendronate group (P=0.01). CONCLUSIONS: The degree of bone loss and the rates of fracture did not differ significantly between the intervention groups. Calcitriol was associated with a higher risk of hypercalciuria. Alendronate-treated patients sustained less bone loss at the spine than those in the reference group, and both intervention groups sustained less bone loss at the hip than the reference group. The requirement for monitoring the serum and urinary calcium levels in calcitriol-treated patients makes alendronate more attractive for the prevention of bone loss early after cardiac transplantation.

Classification of intertrochanteric fractures with computed tomography: a study of intraobserver and interobserver variability and prognostic value.

The purpose of this prospective study was to determine the level of interobserver and intraobserver agreement among orthopedic surgeons and radiologists when computed tomography (CT) scans are used with plain radiographs to evaluate intertrochanteric fractures. In addition, the prognostic value of current classifications systems concerning quality of life was evaluated. Sixty-one patients who presented with intertrochanteric fractures received open reduction and internal fixation with compression hip screw. Three orthopedic surgeons and 2 radiologists independently classified the fractures according to 2 systems: Evans-Jensen and AO (Arbeitsgemeinschaft für Osteo-synthesefragen). Fractures were initially graded with plain radiographs and then again in conjunction with CT. Results were analyzed using the (kappa) kappa coefficient. The 36-item Short-Form Health Survey was administered at baseline, 3 months, and 1 year, and results were correlated with fracture grade. Mean kappa coefficients when comparing radiography alone with radiography and CT scan were 0.63 for the AO system and 0.59 for the Evans-Jensen system. Both represent "fair" agreements. Mean overall interobserver kappa coefficients were 0.67 for radiologists and 0.57 for orthopedic surgeons. Radiologists also had higher intraobserver kappa coefficients. No significant relationships were found between follow-up Short Form Health Survey results and intraoperative grading of fractures. When these classification schemes are compared, interobserver agreement does not appear to change dramatically when information from CT scans is added. This may suggest that (1) more data have been provided by CT with greater possibilities for misinterpretation and (2) these classification schemes may not be comprehensive in describing fracture pattern and displacement. Finally, both systems failed to provide any prognostic value.