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

Orthopedic treatment of hip fracture

There are those who advocate nonoperative treatment of impacted femoral neck fractures, but in general there is consensus that surgery is the treatment of choice for both trochanteric hip fracture and femoral neck fracture. As for trochanteric fractures, modern results after internal fixation are characterized by only a low percentage of secondary operations, even for unstable fractures and when full weight bearing is permitted immediately after operation. The high rates of complication after internal fixation of femoral neck fractures and the insignificant improvement of these results over the decades have made prosthetic replacement an alternative method of treatment, at least for dislocated femoral neck fractures. Until a quantifiable prognostic method to judge whether a given femoral neck fracture will heal is available, and until sufficiently large, prospective techniques have been undertaken, diverging opinions about the operative treatment of choice will persist

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

Histology of impacted bone-graft incorporation

We describe the histologic findings of 31 tissue samples from 21 cases in 19 different patients taken 1 to 48 months after revision arthroplasty and impaction grafting in the hip (Lubinus SP-II prosthesis Waldemar Link, Hamburg, Germany, or Charnley Elite prosthesis, Johnson & Johnson, New Brunswick, NJ) and the knee (Link Rotation Knee Waldemar Link). One month after surgery, a fibrous stroma and some newly formed woven bone were found in the graft bed. After 4 months, many of the dead trabeculae in the graft bed had layers of living bone and osteoid in all samples. These layers, indicating a gradual ingrowth of living bone, increased over time. In the proximal end of the femur examined after 48 months, a significant proportion of the graft bone remained dead, whereas in the rest of the femur, the bone healing was complete. A similar but possibly less frequent bone formation was found in the 2 cases evaluated after a revision total knee arthroplasty combined with impaction grafting