Bone turnover markers are correlated with total skeletal uptake of 99mTc-methylene diphosphonate (99mTc-MDP)

ABSTRACT: BACKGROUND: Skeletal uptake of 99mTc labelled methylene diphosphonate (99mTc-MDP) is used for producing images of pathological bone uptake due to its incorporation to the sites of active bone turnover. This study was done to validate bone turnover markers using total skeletal uptake (TSU) of 99mTc-MDP. METHODS: 22 postmenopausal women (52-80 years) volunteered to participate. Scintigraphy was performed by injecting 520 MBq of 99mTc-MDP and taking whole body images after 3 minutes, and 5 hours. TSU was calculated from these two images by taking into account the urinary loss and soft tissue uptake. Bone turnover markers used were bone specific alkaline phosphatase (S-Bone ALP), three different assays for serum osteocalcin (OC), tartrate resistant acid phosphatase 5b (S-TRACP5b), serum C-terminal cross-linked telopeptides of type I collagen (S-CTX-I) and three assays for urinary osteocalcin (U-OC). RESULTS: The median TSU of 99mTc-MDP was 23% of the administered activity. All bone turnover markers were significantly correlated with TSU with r-values from 0.52 (p = 0.013) to 0.90 (p < 0.001). The two resorption markers had numerically higher correlations (S-TRACP5b r = 0.90, S-CTX-I r = 0.80) than the formation markers (S-Total OC r = 0.72, S-Bone ALP r = 0.66), but the difference was not statistically significant. TSU did not correlate with age, weight, body mass index or bone mineral density. CONCLUSION: In conclusion, bone turnover markers are strongly correlated with total skeletal uptake of 99mTc-MDP. There were no significant differences in correlations for bone formation and resorption markers. This should be due to the coupling between formation and resorption

Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)α agonist fenofibrate and the PPARγ agonist pioglitazone

<p>Abstract</p> <p>Background</p> <p>All the peroxisome proliferator activated receptors (PPARs) are found to be expressed in bone cells. The PPARγ agonist rosiglitazone has been shown to decrease bone mass in mice and thiazolidinediones (TZDs) have recently been found to increase bone loss and fracture risk in humans treated for type 2 diabetes mellitus. The aim of the study was to examine the effect of the PPARα agonist fenofibrate (FENO) and the PPARγ agonist pioglitazone (PIO) on bone in intact female rats.</p> <p>Methods</p> <p>Rats were given methylcellulose (vehicle), fenofibrate or pioglitazone (35 mg/kg body weight/day) by gavage for 4 months. BMC, BMD, and body composition were measured by DXA. Histomorphometry and biomechanical testing of excised femurs were performed. Effects of the compounds on bone cells were studied.</p> <p>Results</p> <p>The FENO group had higher femoral BMD and smaller medullary area at the distal femur; while trabecular bone volume was similar to controls. Whole body BMD, BMC, and trabecular bone volume were lower, while medullary area was increased in PIO rats compared to controls. Ultimate bending moment and energy absorption of the femoral shafts were reduced in the PIO group, while similar to controls in the FENO group. Plasma osteocalcin was higher in the FENO group than in the other groups. FENO stimulated proliferation and differentiation of, and OPG release from, the preosteoblast cell line MC3T3-E1.</p> <p>Conclusion</p> <p>We show opposite skeletal effects of PPARα and γ agonists in intact female rats. FENO resulted in significantly higher femoral BMD and lower medullary area, while PIO induced bone loss and impairment of the mechanical strength. This represents a novel effect of PPARα activation.</p

Commissioning and performance of the CMS silicon strip tracker with cosmic ray muons

This is the Pre-print version of the Article. The official published version of the Paper can be accessed from the link below - Copyright @ 2010 IOPDuring autumn 2008, the Silicon Strip Tracker was operated with the full CMS experiment in a comprehensive test, in the presence of the 3.8 T magnetic field produced by the CMS superconducting solenoid. Cosmic ray muons were detected in the muon chambers and used to trigger the readout of all CMS sub-detectors. About 15 million events with a muon in the tracker were collected. The efficiency of hit and track reconstruction were measured to be higher than 99% and consistent with expectations from Monte Carlo simulation. This article details the commissioning and performance of the Silicon Strip Tracker with cosmic ray muons.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Prediction of bone loss using biochemical markers of bone turnover.

The association between baseline levels of eleven bone turnover markers and 5-year rate of bone density change was prospectively studied in a population-based sample of 601 75-year-old women. Several bone formation and resorption markers as well as urinary osteocalcin were modestly correlated to rate of bone density change. Introduction Prediction of bone loss by bone turnover markers (BTMs) has been investigated with conflicting results. There is limited information in the elderly. Methods Eleven bone turnover markers were analyzed in 75year old women in the OPRA study (n= 601) and compared to the 5-year change of areal bone mineral density (aBMD) in seven skeletal regions. Results Annual aBMD change varied between +0.4% ( spine) and -2.0% ( femoral neck). Significant associations (p < 0.01) were found for four different serum osteocalcins (S-OCs) ( standardized regression coefficient -0.20 to -0.22), urinary deoxypyridinoline (-0.19), serum TRACP5b (-0.19), serum CTX- I (-0.21), two of the three urinary osteocalcins (U-OCs) (-0.16) and aBMD change of the leg region ( derived from the total body measurement). After adjustment for baseline aBMD, associations were found for all S-OCs (-0.11 to -0.16), two of the three U-OCs (-0.14 to -0.16) and aBMD change at the total hip, and for three of the four S-OCs (-0.14 to -0.15), S-TRACP5b (-0.11), two of the three U-OCs (-0.14 to -0.15) and aBMD change at the femoral neck. There were no significant results concerning aBMD change at the spine. Conclusion This study indicates that BTMs are correlated with aBMD loss in some skeletal regions in elderly women

The ankle fracture as an index of future fracture risk : A 25-40 year follow-up of 1063 cases

In 1992 a retrospective case control study was performed, based on all patients with ankle fractures (n 1063) treated at the Department of Orthopedics in Malmö Sweden, between 1950-1951 and 1961-1965. As all radiographic examinations have been saved in Malmö we were able to study all subsequent fractures that this group had sustained. 260 patients from 1961-1965 who were still living in Malmö today were also compared with an age-and gender-matched control group regarding the location and type of subsequent fractures. the group with former ankle fractures continued to have a two-fold increased incidence of all sorts of fractures. the same result was found when looking at the upper and lower extremities separately. However, the risk of sustaining new fractures in the once-fractured extremity was not increased compared to the uninjured side

Importance of bone graft quality for implant integration after maxillary sinus reconstruction

OBJECTIVE: The aim of this study was to determine whether bone quality, as assessed by osteometry and histologic parameters, can be used to predict implant integration in conjunction with maxillary sinus reconstruction. STUDY DESIGN: Twelve patients with severely atrophied maxillary alveolar processes were treated through use of a two-stage surgical reconstructive strategy with implant placement 4 months after bone grafting. Bone biopsy specimens taken from the iliac crest peroperatively and from the sinus inlay sites 1, 2, 4, 6, or 12 months postoperatively were analyzed by light microscopy and osteomorphometry. Bone mineral content was measured by osteometry. RESULTS: Osteometric and osteomorphometric data (trabecular bone volume [%], assessment of chromatin staining, and an osteocyte index) registered for the biopsy specimens were not statistically correlated with implant failure. CONCLUSIONS: Prognostic evaluation of implant survival is difficult. The tested methods did not contribute to the improvement of guidelines for the clinical handling of these patients

Changes of bone mineral mass and soft tissue composition after hip fracture

The aim of this prospective longitudinal study was to measure prospectively the bone mineral density (BMD) and anthropometric variables after a hip fracture. In particular, we studied changes in the BMD in both the injured and uninjured hips, and examined if the postoperative mortality rate and complications, including pseudarthrosis of the fracture and late segmental collapse of the head of the femur, could be predicted by early bone mass measurements. The bone mineral density and the body composition were measured with dual energy X-ray absorptiometry in 102 consecutive hip fracture patients, 31 men and 71 women, with a mean age of 74 and 79 years, respectively. All cases were operated on within 3 days. The measurements were undertaken within 10 days after the fracture, after 4 and after 12 months. The BMD of the hip fracture cases decreased, especially in the lower extremities where the patients lost 7%, during the first year after the fracture. The patients also lost lean body mass (5%) but gained fat (11%) during the same period. They lost significantly more bone mass in the fractured hip than in the uninjured hip (p < 0.05). No difference was found between those patients who survived and those who died within 2 years after their hip fracture in neither the initial measurement nor in the follow-up measurements. Also, we found no difference between those patients whose hip fracture healed and those who developed late segmental collapse or pseudarthrosis. In conclusion, osteoporotic hip fracture cases lose bone mass at an increased rate, especially in the fractured hip. Also, their soft tissue composition changes, gaining fat while losing muscle mass. Furthermore, it seems that early bone mineral measurements cannot predict postoperative failures or postoperative mortality

Vitamin D deficiency and ovariectomy reduced the strength of the femoral neck in rats

Vitamin D (vit D) deficiency is common in the elderly, and the aim of this study was to investigate whether vit D deprivation in ovariectomized (ovx) and normal rats would reduce fracture strength. Forty mature female Wistar rats were randomized into four groups: two were ovariectomized (ovx) and two were sham-operated (sham). One ovx and one sham group were fed a vit D-deficient diet (Ovx-D and Sham-D), and the control groups were fed normal rat chow (Ovx and Sham) for 12 weeks. Vit D deficiency was substantiated after 12 weeks by undetectable serum concentrations of 25OHD in the Sham-D and Ovx-D groups. 85Sr activity was lower in Sham-D than in the other groups (P < 0.005). Tibial and femoral weights and lengths showed no differences. Distal tibial trabecular bone volume was reduced in both ovx groups compare with sham (P < 0.005). Bone mineral density (BMD) was higher in sham than in Sham-D and both ovx groups (P < 0.005). Femoral area moment of inertia increased and ultimate stress decreased in Ovx-D compared with ovx (P < 0.05). Other biomechanical properties of the femoral shafts did not differ significantly. The femoral neck was significantly weaker in Ovx-D than in the other groups. In conclusion, ovx decreased tibial trabecular bone volume and both ovx and vit D depletion reduced femoral BMD in rats. Vit D depletion reduced the ultimate stress in the femoral shaft, and the combined depletion of estrogen and vit D significantly reduced the fracture strength in the femoral neck. This fits well with clinical evidence of how postmenopausal status combined with vit D deficiency lead to an increased risk of hip fractures, making this animal model a possible tool for investigating measures to prevent such fractures