Minimally-invasive osteotome sinus floor elevation combined with short implants and platelet-rich plasma for edentulous atrophic posterior maxilla: a five-year follow-up prospective study.

The aim of this study was to investigate the success of the combination of short implants, osteotome sinus floor elevation technique (OSFE) and pure platelet rich plasma (P-PRP), for the rehabilitation of atrophic posterior maxilla. Fifty-one patients were included in this study, receiving a total of 88 short implants in three different lengths (6.5 mm, 7.5 mm, 8.5 mm), depending on the residual bone height level. A total of 39 standard implants were also inserted when judged necessary, and splinted with one or more short implants in order to support a fixed prosthesis. Data were recorded in a one-year and five- year follow-ups. No statistically significant difference was found between short implants with different length, nor between short and standard length implants in terms of both bone level change and bone height. Based on the present results, the use of short implants combined with OSFE technique for the rehabilitation of atrophic posterior maxilla can be recommended.

Flocked nylon swabs versus RODAC plates for detection of multidrug-resistant organisms on environmental surfaces in intensive care units.

To compare two culture methods [nylon fiber flocked swabs with broth enrichment versus RODAC ('replicate organism detection and counting') plates] for recovery of multidrug-resistant organisms, 780 environmental surfaces in 63 rooms of patients on contact precautions in four intensive care units at one hospital were examined. Among sites that had at least one positive culture, swab culture with broth enrichment detected the target organisms more frequently than RODAC plates (37.5% vs 26.0%, P = 0.06). There was moderate agreement between the two methods (κ = 0.44) with agreement better for small or flat surfaces compared to large or irregular surfaces.

Platelet transfusion: a clinical practice guideline from the AABB

BACKGROUND: The AABB (formerly, the American Association of Blood Banks) developed this guideline on appropriate use of platelet transfusion in adult patients. METHODS: These guidelines are based on a systematic review of randomized, clinical trials and observational studies (1900 to September 2014) that reported clinical outcomes on patients receiving prophylactic or therapeutic platelet transfusions. An expert panel reviewed the data and developed recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RECOMMENDATION 1: The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 2: The AABB suggests prophylactic platelet transfusion for patients having elective central venous catheter placement with a platelet count less than 20 × 109 cells/L. (Grade: weak recommendation; low-quality evidence). RECOMMENDATION 3: The AABB suggests prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 4: The AABB suggests prophylactic platelet transfusion for patients having major elective nonneuraxial surgery with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 5: The AABB recommends against routine prophylactic platelet transfusion for patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass. The AABB suggests platelet transfusion for patients having bypass who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction. (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 6: The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous). (Grade: uncertain recommendation; very-low-quality evidence).(AU)

Post-flood measurement of fungal bio-aerosol in a resource-limited hospital: can the settle plate method be used?

The performance of the settle plate method (SPM) compared with the microbiological air sampler method (MAS) for post-flood fungal bio-aerosol (FB) measurement was evaluated in a Thai hospital. Compared with closed-ventilation units, open-ventilation units had significantly higher median FB level by SPM on days 3 and 5 of incubation (270 vs 90 colony-forming units (cfu)/m(3) and 420 vs 180 cfu/m(3), respectively). Strong correlations between SPM and MAS results on day 3 (r = 1.60, P < 0.001) and day 5 (r = 1.49, P = 0.002) of incubation suggested the utility of SPM for post-flood FB measurement in open-ventilation units in resource-limited situations.

Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial.

UNLABELLED: In a phase 2 study, continued denosumab treatment for up to 8 years was associated with continued gains in bone mineral density and persistent reductions in bone turnover markers. Denosumab treatment was well tolerated throughout the 8-year study. INTRODUCTION: The purpose of this study is to present the effects of 8 years of continued denosumab treatment on bone mineral density (BMD) and bone turnover markers (BTM) from a phase 2 study. METHODS: In the 4-year parent study, postmenopausal women with low BMD were randomized to receive placebo, alendronate, or denosumab. After 2 years, subjects were reallocated to continue, discontinue, or discontinue and reinitiate denosumab; discontinue alendronate; or maintain placebo for two more years. The parent study was then extended for 4 years where all subjects received denosumab. RESULTS: Of the 262 subjects who completed the parent study, 200 enrolled in the extension, and of these, 138 completed the extension. For the subjects who received 8 years of continued denosumab treatment, BMD at the lumbar spine (N = 88) and total hip (N = 87) increased by 16.5 and 6.8 %, respectively, compared with their parent study baseline, and by 5.7 and 1.8 %, respectively, compared with their extension study baseline. For the 12 subjects in the original placebo group, 4 years of denosumab resulted in BMD gains comparable with those observed during the 4 years of denosumab in the parent study. Reductions in BTM were sustained over the course of continued denosumab treatment. Reductions also were observed when the placebo group transitioned to denosumab. Adverse event profile was consistent with previous reports and an aging cohort. CONCLUSION: Continued denosumab treatment for 8 years was associated with progressive gains in BMD, persistent reductions in BTM, and was well tolerated.

Evaluation of chlorhexidine 0.05% with the adjunct of fluoride 0.05% in the inhibition of plaque formation: a double blind, crossover, plaque regrowth study.

OBJECTIVE: The aim of this study was to evaluate the effect of mouthrinses containing 0.05% chlorhexidine + 0.05% fluoride solution on early dental plaque regrowth. MATERIALS AND METHODS: Thirty periodontally healthy subjects were included in the study. A crossover 4-day plaque regrowth protocol was adopted. The test product was initially used in 15 patients, while a placebo was administered to the other 15 patients. Then, after a washout period, each patient used the other product. No other oral hygiene manoeuvre was allowed. Full-mouth plaque and bleeding scores (FMPS and FMBS) were evaluated at baseline and after 4 days. RESULTS: All subjects completed the study. The mean age was 27 ± 8.4 years. Five patients were smokers with a mean daily consumption of 1 ± 2.5 cigarettes. FMPS at baseline was 8.0 ± 4.4 for control group and 7.9 ± 3.8 for test group, without significant difference. After the 4-day plaque regrowth the mean FMPS significantly increased to 31.9 ± 16.5 and 36.3 ± 16.1 for control and test group, respectively (no significant difference between the two groups). CONCLUSIONS: The test product was safe and well tolerated by subjects. The similar outcomes of the two experimental groups suggest that the two products have an equivalent effect on early dental plaque regrowth. Studies with longer follow-up are needed to clarify whether there is a beneficial long-term effect of daily rinses with the tested solution.

A novel approach for x-ray scattering experiments in magnetic fields utilizing trapped flux in type-II superconductors.

We introduce a novel approach to x-ray scattering studies in applied magnetic fields by exploiting vortices in superconductors. This method is based on trapping magnetic flux in a small disk-shaped superconductor (known as a trapped field magnet, TFM) with a single-crystal sample mounted on or at close proximity to its surface. This opens an unrestricted optical access to the sample and allows magnetic fields to be applied precisely along the x-ray momentum transfer, facilitating polarization-sensitive experiments that have been impractical or impossible to perform to date. The TFMs used in our study remain stable and provide practically uniform magnetic fields for days, which are sufficient for comprehensive x-ray diffraction experiments, specifically x-ray resonance exchange scattering (XRES) to study field-induced phenomena at a modern synchrotron source. The TFM instrument has been used in a "proof-of-principle" XRES study of a meta-magnetic phase in a rare-earth compound, TbNi(2)Ge(2), in order to demonstrate its potential.

Issues in modern bone histomorphometry.

This review reports on proceedings of a bone histomorphometry session conducted at the Fortieth International IBMS Sun Valley Skeletal Tissue Biology Workshop held on August 1, 2010. The session was prompted by recent technical problems encountered in conducting histomorphometry on bone biopsies from humans and animals treated with anti-remodeling agents such as bisphosphonates and RANKL antibodies. These agents reduce remodeling substantially, and thus cause problems in calculating bone remodeling dynamics using in vivo fluorochrome labeling. The tissue specimens often contain few or no fluorochrome labels, and thus create statistical and other problems in analyzing variables such as mineral apposition rates, mineralizing surface and bone formation rates. The conference attendees discussed these problems and their resolutions, and the proceedings reported here summarize their discussions and recommendations.

Prognostic value of post-thyroidectomy thyroglobulin levels in patients with differentiated thyroid cancer.

BACKGROUND: Thyroglobulin is an excellent biological marker of persistent or recurrent thyroid cancer during long-term follow-up. Most studies investigated its diagnostic value but not its prognostic value over time. We aim to study the prognostic value of thyroglobulin levels early after total thyroidectomy, before iodine ablation. METHODS: The study was based on the Rabin Medical Center registry of patients with non-medullary thyroid carcinoma. Data were collected on the clinical, laboratory, and outcome characteristics of 420 consecutive patients followed at our institution for whom early post-operative pre-ablation thyroglobulin values (baseline thyroglobulin) were available. RESULTS: Patients were classified into 4 groups by baseline thyroglobulin level: 0-2, 2-10, 10-100, and >100 ng/ml. Higher levels were associated with a shift toward male gender (p=0.01), larger tumor size (p=0.02), and a more extensive disease (p<0.0001). They were also related to disease persistence and evidence of disease at last follow-up (p<0.0001). The 10 ng/ml cut-off level identified patients with persistent disease with a sensitivity and specificity of 73%, positive predictive value of 43%, and negative predictive value of 89%. On multivariate analysis, the following variables were predictive of persistent disease: baseline thyroglobulin level, male gender, lymph-node involvement, distant metastases, higher tumor invasiveness, and larger tumor size. However, the predictive power of baseline thyroglobulin level was relatively weak (odds ratio 1.002, 95% confidence interval 1.00-1.04). CONCLUSIONS: In patients with well-differentiated thyroid cancer, a post-thyroidectomy thyroglobulin level <10 ng/ml is associated with a low probability of having persistent disease and can be used combined with other disease characteristics for decisions regarding treatment and follow-up.

A guide to interpreting economic studies in infectious diseases.

Healthcare providers continue to seek improved methods for preventing, detecting and treating diseases that affect human survival and quality of life. At the same time, there will always be financial constraints because of limited societal resources. Many of the discussions on how to provide economically sound solutions to this challenge have not fully engaged the input of clinicians in the field. The purpose of this review is to increase economic knowledge for clinicians. We cover healthcare cost elements and methods used to assign value to a health outcome. We outline the challenges in conducting economic studies in the field of infectious diseases. Finally, we discuss the meaning of efficiency from multiple perspectives, and how the concept of economic externalities applies to infectious diseases.

Clinically silent chromaffin-cell tumors: Tumor characteristics and long-term prognosis in patients with incidentally discovered pheochromocytomas.

BACKGROUND: Chromaffin-cell tumors (CCT), a rare group of catecholamine producing endocrine neoplasms, are traditionally suspected and diagnosed in patients presenting with episodic hypertension, together with the classic triad of headache, sweating, and tachycardia. Asymptomatic CCT are increasingly diagnosed, frequently as "incidentalomas". We have conducted a multicenter retrospective study, to assess the characteristics of a group of patients with clinically silent CCT, compared with a group of patients with typical CCT. METHODS: Forty-three consecutive patients with CCT (24 with silent and 19 with typical tumors) have been retrospectively studied for a period of up to 20 yr (between 1989 and 2009); clinical picture, biochemical tests, as well as topographic and functional assessment were analyzed at diagnosis and periodically following treatment. Surgical samples were reviewed for neuroendocrine markers and for signs of invasiveness. RESULTS: Patients with clinically silent CCT were significantly older than the typical ones (56.3±3.4 vs 48.0±4.8 yr; p<0.05); 15 of them (63%) were completely asymptomatic, and 9 patients (37%) complained of non-specific abdominal symptoms. Hypertension was present in only 6 silent CCT patients (25%), it was well controlled [mean blood pressure (BP) 134/84 mmHg], and persisted after surgery in only 2 patients. Fourteen out of twenty-four silent CCT patients (58%) were managed pre-operatively with prophylactic combination of α and ß blockade, despite normal BP values. Clinically silent CCT were larger than typical CCT (mean diameter of 5.2±2.3 cm vs 4.6±1.5 cm, p<0.05) and secreted higher a mounts of normeta neph rines. All clinically silent CCT patients were defined as "cured" after surgery. CONCLUSION: Clinically silent CCT are more prevalent than previously reported. With an adequate pre-surgical diagnosis and patient preparation, the prognosis of silent tumors is usually excellent.

Quality of life after microscopic periradicular surgery using two different incision techniques: a randomized clinical study.

AIM: To monitor the quality of life of patients after periradicular surgery when two different flap designs were used. METHODOLOGY: Forty patients with teeth having a periradicular lesion of endodontic origin were included according to specific selection criteria. Patients were randomly assigned to two groups. In one group a sulcular incision (SI) with complete papilla mobilization was made, and in the other group a papilla-base incision (PBI) was used. Periradicular surgery was performed using a surgical microscope. Parameters related to life quality were recorded daily in the first week post-surgery using a questionnaire. Pain was evaluated with a 0-100 visual analog scale (VAS). Other symptoms (swelling, bleeding and nausea), plus functions (chewing, speaking, sleeping, daily routine and work) were assessed using a five-point scale. Analgesic intake was recorded. Fisher's test and unpaired t-test were used to assess the difference between groups. RESULTS: The VAS score for pain, and the scores for swelling, chewing and phonetic impairment, peaked on days 1 and 2 postoperatively. A significant difference in favour of the PBI group was found for chewing and swelling in the first 4 days. Starting from day 3 post-surgery, the PBI group reported a significantly more rapid decrease in pain levels and analgesics use than the SI group (P < 0.05). The other parameters were similar in the two groups. CONCLUSIONS: The papilla-base incision technique may be preferred as reduction of pain levels, swelling and drug intake were more rapid in the first week postoperatively compared with cases in which a sulcular incision was used.

Interventional evaluation of environmental contamination by vancomycin-resistant enterococci: failure of personnel, product, or procedure?

It is not clear whether improvement in environmental decontamination is more efficiently achieved through changes in cleaning products, cleaning procedures, or performance of cleaning personnel. To assess the impact of cleaning performance on environmental contamination with vancomycin-resistant enterococci (VRE), we conducted a sequential trial in which a multifaceted environmental cleaning improvement intervention was introduced in a medical intensive care unit and respiratory step-down unit. The intervention included educational lectures for housekeepers and an observational programme of their activities without changes in cleaning products or written procedures. Following these interventions, the proportion of environmental sites cleaned improved from 49% to 85% (P<0.001); contamination of environmental sites declined from 21% to 8% (P<0.0001) before cleaning and from 13% to 8% (P<0.0001) after cleaning. The improved cleaning and contamination rates persisted in a washout period. In a multivariate model, cleaning thoroughness strongly influenced the degree of environmental contamination, with a 6% decline in VRE prevalence with every 10% increase in percentage of sites cleaned. These findings suggest that surface contamination with VRE is due to a failure to clean rather than to a faulty cleaning procedure or product.

Spectroscopic markers of bone quality in alendronate-treated postmenopausal women.

UNLABELLED: Comparison of infrared spectroscopic images of sections from biopsies of placebo-treated post-menopausal women and women treated for 3 years with 10 mg/day alendronate demonstrated significant increases in cortical bone mineral content, no alterations in other spectroscopic markers of "bone quality," but a decrease in tissue heterogeneity. METHODS: The material properties of thick sections from iliac crest biopsies of seven alendronate-treated women were compared to those from ten comparably aged post-menopausal women without bone disease, using infrared spectroscopic imaging at approximately 7 microm spatial resolution. Parameters evaluated were mineral/matrix ratio, crystallinity, carbonate/amide I ratio, and collagen maturity. The line widths at half maximum of the pixel histograms for each parameter were used as measures of heterogeneity. RESULTS: The mineral content (mineral/matrix ratio) in the cortical bone of the treated women's biopsies was higher than that in the untreated control women. Crystallinity, carbonate/protein, and collagen maturity indices were not significantly altered; however, the pixel distribution was significantly narrowed for all cortical and trabecular parameters with the exception of collagen maturity in the alendronate treatment group. CONCLUSIONS: The increases in mineral density and decreased fracture risk associated with bisphosphonate treatment may be counterbalanced by a decrease in tissue heterogeneity, which could impair tissue mechanical properties. These consistent data suggest that alendronate treatment, while increasing the bone mass, decreases the tissue heterogeneity.

Microscope versus endoscope in root-end management: a randomized controlled study.

The purpose of this prospective, randomized, clinical study was to monitor the outcome of periradicular surgery, in which either a surgical microscope or an endoscope was used as a magnification device. A total of 113 teeth in 70 patients were included in the study, according to specific selection criteria. The choice of endoscope or surgical microscope was made using a randomized table. One hundred cases were followed for at least 2 years. Of these, 59 root-end management procedures were performed using a microscope and 41 using an endoscope. At the 2-year follow-up they were classified into three groups (success, uncertain healing and failure) according to radiographic and clinical criteria. After a 2-year follow-up, 91 teeth (91%) healed successfully. In the group using an endoscope 90% of successful healing was achieved, while 92% of success was recorded for the group using a microscope. No statistically significant difference was found in the treatment results relating to the type of magnification device. The type of magnification device used did not seem to affect the outcome of endodontic surgery.

Human adipose-derived stem cells as future tools in tissue regeneration: osteogenic differentiation and cell-scaffold interaction.

Tissue engineering is now contributing to new developments in several clinical fields, and mesenchymal stem cells derived from adipose tissue (hASCs) may provide a novel opportunity to replace, repair and promote the regeneration of diseased or damaged musculoskeletal tissue. Our interest was to characterize and differentiate hASCs isolated from twenty-three donors. Proliferation, CFU-F, cytofluorimetric and histochemistry analyses were performed. HASCs differentiate into osteogenic, chondrogenic, and adipogenic lineages, as assessed by tissue-specific markers such as alkaline phosphatase, osteopontin expression and deposition of calcium matrix, lipid-vacuoles formation and Glycosaminoglycans production. We also compared osteo-differentiated hASCs cultured on monolayer and loaded on biomaterials routinely used in the clinic, such as hydroxyapatite, cancellous human bone fragments, deproteinized bovine bone granules, and titanium. Scaffolds loaded with pre-differentiated hASCs do not affect cell proliferation and no cellular toxicity was observed. HASCs tightly adhere to scaffolds and differentiated-hASCs on human bone fragments and bovine bone granules produced, respectively, 3.4- and 2.1-fold more calcified matrix than osteo-differentiated hASCs on monolayer. Moreover, both human and deproteinized bovine bone is able to induce osteogenic differentiation of CTRL-hASCs. Although our in vitro results need to be confirmed in in vivo bone regeneration models, our data suggest that hASCs may be considered suitable biological tools for the screening of innovative scaffolds that would be useful in tissue engineering.

Surgical versus non-surgical endodontic re-treatment for periradicular lesions.

BACKGROUND: Though success rates of endodontic initial treatment have been improving over the years, persistence of periapical disease is far from being a rare condition. The most common therapeutical options for the re-treatment of teeth with periapical pathosis are non-surgical orthograde treatment and surgical treatment. Selection between alternative treatments should be based on assessment of respective benefits (mainly healing) and risks from studies consistent with a high level of evidence. OBJECTIVES: To test the null hypothesis of no difference in outcome between surgical and non-surgical therapy for endodontic re-treatment of periradicular lesions. SEARCH STRATEGY: The Cochrane Oral Health Group Trials Register, CENTRAL, MEDLINE and EMBASE were searched with appropriate search strategies. Handsearching included eight dental journals. The bibliographies of relevant clinical trials and relevant articles were checked for identifying studies outside the handsearched journals. Seven manufacturers of instruments in the field of endodontics or endodontic surgery or both, as well as the authors of the identified randomised controlled trials (RCTs) were contacted in order to identify unpublished or ongoing RCTs. No language restriction was placed. The last electronic search was conducted on 3rd April 2007. SELECTION CRITERIA: All RCTs about re-treatment of teeth with periapical pathosis in which both surgical and non-surgical approaches were used and having a follow up of at least 1 year were considered for the analysis. DATA COLLECTION AND ANALYSIS: A quality assessment of the included RCTs was carried out and the authors were contacted for missing information. We independently extracted the data in duplicate. We followed the Cochrane Oral Health Group's statistical guidelines. MAIN RESULTS: Three RCTs were identified, two of them reporting different data from the same clinical study. The risk of bias was judged as moderate for one study and high for the other one. 126 cases were followed up for at least 1 year, and 82 had a follow up of 4 years. At the 1-year follow up the success rate for surgical treatment was slightly better than non-surgical (risk ratio (RR) 1.13; 95% confidence interval (CI) 0.98 to 1.30). When the follow up was extended to 4 years (only one RCT made it) the outcome for the two procedures became similar. AUTHORS' CONCLUSIONS: The finding that healing rates can be higher for cases treated surgically as compared to those treated non-surgically, at least in the short term, is based on two RCTs only. A single RCT reported that in the medium to long term healing rates for the two procedures are very similar. There is currently scarce evidence for a sound decision making process among alternative treatments for the re-treatment of a periradicular pathosis. More well-designed RCTs should be performed with follow up of at least 4 years, and with a consistent sample size, to detect a true difference in the long term between the outcomes of the two alternative treatments, if any exist.

Endoscopic periradicular surgery: a prospective clinical study.

We did apicectomies of 30 teeth with periradicular lesions in 23 patients, using a 3 mm endoscope. Two patients failed to attend for postoperative assessment and of the remaining 21 patients who had 28 teeth treated the operation was judged after 1 year to be a success in 26 (93%).

Telemedicine and telepresence for trauma and emergency care management.

The use of telemedicine is long-standing, but only in recent years has it been applied to the specialities of trauma, emergency care, and surgery. Despite being relatively new, the concept of teletrauma, telepresence, and telesurgery is evolving and is being integrated into modern care of trauma and surgical patients. This paper will address the current applications of telemedicine and telepresence to trauma and emergency care as the new frontiers of telemedicine application. The University Medical Center and the Arizona Telemedicine Program (ATP) in Tucson, Arizona have two functional teletrauma and emergency telemedicine programs and one ad-hoc program, the mobile telemedicine program. The Southern Arizona Telemedicine and Telepresence (SATT) program is an inter-hospital telemedicine program, while the Tucson ER-link is a link between prehospital and emergency room system, and both are built upon a successful existing award winning ATP and the technical infrastructure of the city of Tucson. These two programs represent examples of integrated and collaborative community approaches to solving the lack of trauma and emergency care issue in the region. These networks will not only be used by trauma, but also by all other medical disciplines, and as such have become an example of innovation and dedication to trauma care. The first case of trauma managed over the telemedicine trauma program or "teletrauma" was that of an 18-month-old girl who was the only survival of a car crash with three fatalities. The success of this case and the pilot project of SATT that ensued led to the development of a regional teletrauma program serving close to 1.5 million people. The telepresence of the trauma surgeon, through teletrauma, has infused confidence among local doctors and communities and is being used to identify knowledge gaps of rural health care providers and the needs for instituting new outreach educational programs.

Glucocorticoids act directly on osteoclasts to increase their life span and reduce bone density.

Glucocorticoid administration to mice results in a rapid loss of bone mineral density due to an imbalance in osteoblast and osteoclast numbers. Whereas excess glucocorticoids reduce both osteoblast and osteoclast precursors, cancellous osteoclast number surprisingly does not decrease as does osteoblast number, presumably due to the ability of glucocorticoids to promote osteoclast life span. Whether glucocorticoids act directly on osteoclasts in vivo to promote their life span and whether this contributes to the rapid loss of bone with glucocorticoid excess remains unknown. To determine the direct effects of glucocorticoids on osteoclasts in vivo, we expressed 11beta-hydroxysteroid dehydrogenase type 2, an enzyme that inactivates glucocorticoids, specifically in the osteoclasts of transgenic mice using the tartrate-resistant acid phosphatase promoter. Bone mass, geometry, and histomorphometry were similar in untreated wild-type and transgenic animals. Glucocorticoid administration for 7 d caused equivalent increases in cancellous osteoblast apoptosis, and equivalent decreases in osteoblasts, osteoid, and bone formation, in wild-type and transgenic mice. In contrast, glucocorticoids stimulated expression of the mRNA for calcitonin receptor, an osteoclast product, in wild-type but not transgenic mice. Consistent with the previous finding that glucocorticoids decrease osteoclast precursors and prolong osteoclast life span, glucocorticoids decreased cancellous osteoclast number in the transgenic mice but not wild-type mice. In accord with this decrease in osteoclast number, the loss of bone density observed in wild-type mice was strikingly prevented in transgenic mice. These results demonstrate for the first time that the early, rapid loss of bone caused by glucocorticoid excess results from direct actions on osteoclasts.