Differential bone turnover in an angulated fracture model in the rat.

We have developed a simple rat model of angulated tibial fracture which elicits substantial differences in bone formation and resorption within the same bone. In 35 rats the right mid-tibia was manually fractured and fixed with an intramedullary 17-gauge cannula needle. Twenty tibias were fixed in anterior angulation (27 +/- 5 degrees) and 15 in posterior angulation (31 +/- 5 degrees). Serial X-rays were taken over a 12-week period. All fractures healed completely within five weeks. In both groups, bone thickness was already significantly greater on the concave side than on the convex side at week 3 and remained so until the end of the experiment. The thickness on the convex side decreased dramatically within 3 to 5 weeks and gradually thereafter. For morphological analysis of bone mineralization, 3 rats from each group were given calcein and alizarin red injected at different time points up to 14 weeks. Maximum new bone formation was noted within the first 3 weeks. Over the ensuing weeks, new bone formation remained intense on the concave side, but it was virtually absent on the convex side. These results show that angulated fracture deformity reproducibly exhibits differential bone turnover, which can be exploited in research on local regulatory factors. To exemplify the utility of the model, an immunohistochemical study on two local markers was done. Callus tissue of five rats in the anterior angulation group at week 3 post-fracture was stained for the cytokine IL- 1beta, a stimulator of bone resorption, and the neuropeptide CGRP, an inhibitor of resorption, showing clear differences in positive staining between the concave and convex sides. Our in-vivo model offers a means of analyzing morphologically and quantitatively the differential expression and action of factors involved in local bone turnover.

Maintenance of cancellous bone in ovariectomized, human parathyroid hormone [hPTH(1-84)]-treated rats by estrogen, risedronate, or reduced hPTH.

This study compares effects of maintenance doses of human parathyroid hormone [hPTH(1-84)], 17beta-estradiol (E2), and risedronate on distal femur bone mineral density and proximal tibia cancellous bone histomorphometry in ovariectomized (ovx), osteopenic rats previously administered a higher dose of hPTH. Nine groups (n = 8) of 3.5-month-old ovx or intact Sprague-Dawley rats were left untreated for 11 weeks to allow for the development of cancellous osteopenia in the ovx groups. Next, the ovx rats received subcutaneous injections of hPTH (75 microg/kg per day, three times per week) or vehicle for 12 weeks. Treatments were then changed to E2 (10 microg/kg per day, two times per week), risedronate (Ris; 3 microg/kg per day, three times per week), low-dose hPTH(1-84) (LowPTH; 25 microg/kg per day, three times per week), or vehicle, and administered for 36 weeks. The intact control group remained untreated for the duration of study. Femora and tibiae were collected at weeks -11 (baseline); 0 (ovx effect); 12 (hPTH effect), and 24, 36, and 48 (maintenance effects). Endpoints evaluated included distal femur bone mineral density (BMD) and proximal tibia cancellous bone volume (BV/TV), osteoclast surface (Oc.S), mineralizing surface (MS), mineral apposition rate (MAR), and bone formation rate (BFR). Ovariectomy had a negative effect on distal femur BMD and proximal tibia BV/TV. Treatment of ovx rats with hPTH for 12 weeks resulted in higher BMD in comparison to intact controls, and higher cancellous BV/TV in comparison to ovx controls. Discontinuation of hPTH resulted in loss of gained BMD within 24 weeks and loss of gained BV/TV within 12 weeks. Treatment of ovx rats with hPTH for 12 weeks followed by E2 treatment left BMD and BV/TV similar to vehicle-treated ovx rats by week 48 (36 weeks after commencement of the E2 maintenance treatment). Maintenance treatment with risedronate resulted in BMD and BV/TV similar to that of intact controls. Maintenance treatment with low-dose hPTH resulted in greater BMD and similar BV/TV in comparison to intact controls. MS and BFR were highest after low-dose hPTH administration. MS and BFR were lowest after E2 or risedronate, whereas Oc.S was lowest after risedronate administration. Thus, in osteopenic rats, the increment in distal femur BMD and proximal tibia BV/TV gained by 12 weeks of hPTH treatment was lost within 24 and 12 weeks of treatment termination, respectively. Low-dose hPTH maintained BMD and BV/TV after hPTH treatment by stimulating bone formation, whereas risedronate maintained BMD and BV/TV by reducing bone resorption. E2 in a maintenance dose failed to maintain BMD and BV/TV after withdrawal of hPTH treatment.

No effect of verapamil on the local bone response to in vivo mechanical loading.

Verapamil, a calcium channel blocker, alters the intracellular calcium concentration in bone cells in vitro, while mechanical loading stimulates calcium channels. The purpose of this study was to examine the effect of systemic verapamil treatment on the bone response to in vivo external mechanical loading. Female rats (age 5-6 months) were divided into six groups. Half were verapamil treated (0.75 mg/ml drinking water) for 12 weeks. After 8 weeks of treatment, the right tibia was loaded by a four-point bending device. In one set of verapamil and control groups, the right tibia was loaded at 31.8 +/- 0.2 N (36 cycles, 2 Hz, 3 d/wk) for four weeks. A second set was loaded at 40.1 +/- 0.3 N and the third set remained nonloaded. Tibial cortical bone formation and femur bone mineral density (BMD) were evaluated. With loading, bone formation was similarly elevated in loaded tibia of verapamil and control rats (P < 0.003). However, periosteal bone formation (P < 0.001) in the nonloaded tibia, and femoral diaphysis BMD (P < 0.04) were greater in verapamil rats than in controls. We conclude that verapamil, in the dose given, does not interfere with mechanical loading (30, 40 N) at the loaded site and that the voltage-dependent calcium channels, blocked by verapamil, are not significantly involved in the local bone response to increased strain in female rats. However, verapamil increased bone formation and BMD at nonloaded sites of loaded rats. Previously unknown systemic or regional factors associated with loading may explain the potential mechanisms for this interaction and need further investigation.

Maintenance of vertebral body bone mass and strength created by human parathyroid hormone treatment in ovariectomized rats.

The purpose of this cross-sectional study was to evaluate the effects of human parathyroid hormone (1-84) (hPTH) followed by maintenance administration of 17beta-estradiol (E2), risedronate (Ris), or a reduced dose of hPTH (LowPTH) on vertebral body bone mineral density (BMD) and bone strength in ovariectomized (ovx) rats. Eight groups of ovx (219 rats) and one group of intact female rats (48 rats) were left untreated for 11 weeks (age 3.5 months at the beginning). For the following 12 weeks, four ovx groups received subcutaneous injections of hPTH (75 microg/kg per day, 3 days/week) and four groups received vehicle. Treatments were then changed to: E2 (10 microg/kg per day, 2 days/week); Ris (3 microg/kg per day, 3 days/week); LowPTH (25 microg/kg per day, 3 days/week); or vehicle for 36 weeks. Bone tissue was collected at weeks -11 (baseline), 0 (ovx effect), 12 (hPTH effect), 24, 36, and 48 (maintenance effect). The endpoints were vertebral body BMD, ultimate stress (Ultstr), and moduli of elasticity from compression tests (ModM), and from ultrasound tests (ModUS). Ovariectomy resulted in lower BMD (p < 0.001). The hPTH treatment for 12 weeks restored BMD to the level of intact rats. Ultstr and ModUS followed a similar pattern, but the ovx-induced Ultstr was not significant (p = 0.073, ModUS: p = 0.003), nor was the hPTH-induced increase in ModUS (p = 0.131, Ultstr: p = 0.02). After hPTH withdrawal, BMD, Ultstr, and ModUS levels were not different from levels in ovx animals. In Ris-treated rats pretreated with hPTH, BMD (weeks 24 and 48, p < 0.002) and ModUS (week 24, p = 0.018) values were greater than in ovx animals. In LowPTH-treated rats pretreated with hPTH, BMD (weeks 24 and 48, p < 0.001) and Ultstr (week 48, p = 0.005) were greater than in ovx animals. In E(2)-treated rats pretreated with hPTH, BMD was greater than in ovx rats at week 24 (p = 0.009), but did not differ at weeks 36-48. Neither Ultstr nor ModUS in E(2)-treated rats differed significantly from ovx rats at any timepoint. Of the agents and dosing regimens used, we conclude that the hPTH-related vertebral bone mass gain in ovx rats can be maintained for up to 36 weeks with risedronate and low-dose hPTH treatment. Bone strength is maintained by treatment with low-dose hPTH, but only partially maintained with risedronate.

Maintenance of cortical bone in human parathyroid hormone(1-84)-treated ovariectomized rats.

The purpose of this cross-sectional study was to evaluate the effects of human parathyroid hormone(1-84) (hPTH) followed by maintenance treatment with 17beta-estradiol (E(2)), risedronate (Ris), or a reduced dose of hPTH (LowPTH) on cortical bone in the ovariectomized (ovx) rat. Eight groups of ovx and one group of intact female rats (3.5 months) were left untreated for 11 weeks. For the following 12 weeks, four groups received subcutaneous injections of hPTH (75 microg/kg per day on 3 days/week) and four groups received vehicle. Treatments were then changed to E(2) (10 microg/kg per day on 2 days/week), Ris (3 microg/kg per day on 3 days/week), LowPTH (25 microg/kg per day on 3 days/week), or vehicle. Bone tissue was collected at weeks -11 (baseline), 0 (ovx effect), 12 (hPTH effect), 24, 36, and 48 (maintenance effect). Bone mineral density (BMD) and bone mineral content (BMC) of the diaphyseal femur and total cross-sectional area (Tt.Ar), marrow area (Ma.Ar), cortical area (Ct.Ar), and periosteal and endocortical bone formation of the tibia were measured. Ovariectomy resulted in lower BMD (weeks 0-48), unaffected BMC, and greater Tt.Ar (weeks 12 and 36), Ma.Ar (week 48), and Ct.Ar (weeks 0 and 12) compared with intact rats. Endocortical and periosteal bone formation were greater in the ovx than in the intact rats up to 23 weeks postovariectomy. Treatment of ovx rats with hPTH for 12 weeks resulted in greater cortical BMD, BMC, and endocortical bone formation than in intact or ovx controls. In ovx rats pretreated with hPTH and then treated with Ris for 36 weeks, BMD and BMC were greater and Ma.Ar was smaller than in ovx controls. In ovx rats pretreated with hPTH and then treated with LowPTH, BMD, BMC, Ct.Ar, and endocortical bone formation were greater and Ma.Ar was smaller than in ovx controls. Treatment of hPTH-pretreated rats with E(2) for 36 weeks did not affect cortical BMD, BMC, and Ct.Ar, although periosteal bone formation was lower in the E(2) group compared with the ovx group. Thus, in ovariectomized rats, cortical bone gained by 12 weeks of hPTH treatment was maintained for up to 36 weeks by treatment with risedronate or low-dose hPTH, but not with 17beta-estradiol.

Screw positions in femoral neck fractures. Comparison of two different screw positions in cadavers.

To evaluate the influence of different screw positions on the stability of fixation in femoral neck fractures, 30 cadaveric proximal femora were osteotomized and fixed with 2 cannulated screws. The proximal screw was placed either with a posterior cortical support in the femoral neck or centrally, supported only by cancellous bone. The distal screw rested on the femoral calcar. The specimens were tested in bending, using the force at 2 and 5 mm deflection at the osteotomy site and at fracture, as an expression of the stability of fixation. The test sequences were recorded on a x-y plotter and on videotape. Bone density measurements were made at the femoral neck, Ward's triangle, and the trochanter region. Our findings indicate that a posterior position with cortical support for the proximal screw, compared to a central screw position with only cancellous bone support, increases the stability of femoral neck fractures.

Verapamil induces increased bone volume and osteopenia in female rats but has the opposite effect in male rats.

Verapamil inhibits the intestinal absorption of calcium (Ca) and increases serum parathyroid hormone in rats. The effects of verapamil on bone tissue after long-term treatment is, however, not well described. Adult female and male Sprague-Dawley rats received verapamil in their drinking water at a dosage of 0.075 mg/ml (low dose) or 0.75 mg/ml (high dose) for 12 weeks; control rats received only drinking water. All rats were fed a diet containing 0.1% Ca and 0.5% P. In female rats, the amount of bone ash per volume was significantly reduced from 0.742 g/ml in controls to 0.713 g/ml after low-dose treatment of verapamil, and to 0.667 g/ml following high-dose treatment (P less than 0.01). The tibial length was increased from 39.7 mm in controls to 40.3 mm or to 40.7 mm after low or high doses (P less than 0.01). The tibial volume increased from 0.385 ml in controls to 0.397 ml after low doses and to 0.429 ml after high doses (P less than 0.01). In contrast, in male rats the amount of bone ash per volume was significantly increased from 0.578 g/ml in controls to 0.580 g/ml after low doses and to 0.620 g/ml after high doses of verapamil (P less than 0.01). The tibial bone volume in males as decreased from 0.633 ml in controls to 0.641 ml after low doses and to 0.583 ml after high doses (P less than 0.05). The tibial length in the males was not changed by verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Postoperative evaluation of Keller's arthroplasty and arthrodesis of the first metatarsophalangeal joint using the EMED gait analysis system.

The authors examined 10 patients who had arthrodesis at the first metatarsophalangeal joint and 10 patients who had Keller's arthroplasty operation. The EMED gait analysis was used to measure the pressure distribution over the sole of the foot during walking. Arthrodesis group had significantly increased maximum pressure in the first and third metatarsal regions. The Keller arthroplasty group had the lowest maximum pressure in the big toe but it was not significant.

Postoperative pressure under the rheumatic feet.

The authors examined ten seropositive rheumatoid arthritis patients with an EMED gait analysis system in a mean four years after foot surgery and compared that with ten normal subjects who formed a control group. The maximum pressure in the toe regions was almost the same as in the control group. The rheumatoid arthritis group had significantly increased maximum pressure in the first metatarsal and tarsal region.