Tibial Bone Mineral Content Research Articles

The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats.

Growth hormone (GH) is of importance for normal bone remodelling. A recent clinical study demonstrated that MK-677, a member of a class of GH secretagogues (GHSs), increases serum concentrations of biochemical markers of bone formation and bone resorption. The aim of the present study was to investigate whether the GHSs, ipamorelin (IPA) and GH-releasing peptide-6 (GHRP-6), increase bone mineral content (BMC) in young adult female rats. Thirteen-week-old female Sprague-Dawley rats were given IPA (0.5 mg/kg per day; n=7), GHRP-6 (0.5 mg/kg per day; n=8), GH (3.5 mg/kg per day; n=7), or vehicle administered continuously s.c. via osmotic minipumps for 12 weeks. The animals were followed in vivo by dual X-ray absorptiometry (DXA) measurements every 4th week. After the animals were killed, femurs were analysed in vitro by mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. After this, excised femurs and vertebrae L6 were analysed by the use of Archimedes' principle and by determinations of ash weights. All treatments increased body weight and total tibial and vertebral BMC measured by DXA in vivo compared with vehicle-treated controls. However, total BMC corrected for the increase in body weight (total BMC:body weight ratio) was unaffected. Tibial area bone mineral density (BMD, BMC/area) was increased, but total and vertebral area BMDs were unchanged. The pQCT measurements in vitro revealed that the increase in the cortical BMC was due to an increased cross-sectional bone area, whereas the cortical volumetric BMD was unchanged. Femur and vertebra L6 volumes were increased but no effect was seen on the volumetric BMDs as measured by Archimedes' principle. Ash weight was increased by all treatments, but the mineral concentration was unchanged. We conclude that treatment of adult female rats with the GHSs ipamorelin and GHRP-6 increases BMC as measured by DXA in vivo. The results of in vitro measurements using pQCT and Archimedes' principle, in addition to ash weight determinations, show that the increases in cortical and total BMC were due to an increased growth of the bones with increased bone dimensions, whereas the volumetric BMD was unchanged.

Femoral neck is a sensitive indicator of bone loss in immobilized hind limb of mouse.

The present study was carried out to evaluate a unilateral hind limb immobilization model in the mouse. The right legs of male mice (age 10-12 weeks) were immobilized for 3 weeks against the abdomen by an elastic bandage. Body weight decreased significantly during the immobilization. Peripheral quantitative computed tomography (pQCT) analysis showed that the cross-sectional cortical area (CSA), the bone mineral content (BMC), and the bone mineral density (BMD) of the tibial diaphysis were lower in both legs of the immobilized animals than in age-matched controls, but the difference was mainly due to weight reduction. At the tibial metaphysis, CSA, BMC, and BMD were reduced in both legs of the immobilized animals, even after weight adjustment. At the femoral neck, CSA, BMC, and BMD were significantly lower in both legs of the immobilized animals, and the difference between the hind legs of the immobilized animals was also highly significant. The findings of the pQCT study were in good agreement with the changes in mechanical strength. The tibia was a more sensitive indicator of diaphyseal bone weakening than the femur when measuring the bending breaking force of the diaphysis. The femoral neck showed significantly decreased strength, and the difference between the immobilized leg and the contralateral leg was most clearly seen in lateral loading. We conclude that 3 weeks of hind limb immobilization weakened the tibia and femur significantly compared with their contralateral counterparts. The reduction was more significantly seen in the mechanical bending strength than in the pQCT evaluation, and the femoral neck was the most sensitive indicator of bone weakening.

Ground reaction forces, bone characteristics, and tibial stress fracture in male runners.

Tibial stress fracture is a common overuse running injury resulting from repetitive mechanical loading. This research project aimed to determine whether runners with a history of tibial stress fracture (TSF) differ in tibial bone geometry, tibial bone mass, and ground reaction force (GRF) parameters during running from those who have never sustained a stress fracture (NSF). Forty-six male running athletes (23 TSF; 23 NSF) ranging in age from 18 to 42 yr were recruited for this cross-sectional study. A force platform was used to measure selected GRF parameters (peak and time to peak for vertical impact force, vertical active force, and horizontal braking force) during running at 4.0 m x s(-1). Tibial bone geometry (cross-sectional dimensions and area) was calculated from a computerized tomography (CT) scan at the junction of the middle and distal thirds. Dual energy x-ray absorptiometry (DXA) provided measurements of tibial bone area, bone mineral content (BMC), and bone mineral density (BMD). The TSF group had significantly smaller tibial cross-sectional area (P = 0.02) and DXA tibial bone area (P = 0.02), after adjusting for height and weight, than the NSF group. There were no significant differences between groups for GRF, tibial BMC, or tibial BMD. These findings support the contention that bone geometry plays a role in stress fracture development and that male athletes with smaller bones in relation to body size are at greater risk for this bony injury.

Intermittent parathyroid hormone (1-34) treatment increases callus formation and mechanical strength of healing rat fractures.

The influence of intermittent parathyroid hormone (PTH(1-34)) administration on callus formation and mechanical strength of tibial fractures in rats was investigated after 20 and 40 days of healing. A dose of 60 microg of PTH(1-34)/kg/day and 200 microg of PTH(1-34)/kg/day, respectively, was administered during the entire periods of healing, and control animals with fractures were given vehicle. The dose of 200 microg of PTH(1-34)/kg/day increased the ultimate load and the external callus volume of the fractures by 75% and 99%, respectively, after 20 days of healing and by 175% and 72%, respectively, after 40 days of healing. The dose of 60 microg of PTH(1-34)/kg/day did not influence either ultimate load or external callus volume of the fractures after 20 days of healing, but the ultimate load was increased by 132% and the external callus volume was increased by 42% after 40 days of healing. During the healing period, the callus bone mineral content (BMC) increased in all groups. After 40 days of healing, the callus BMC was increased by 108% in the 200 microg of PTH(1-34)/kg/day group and by 76% in the 60 microg of PTH(1-34)/kg/day group. Both doses of PTH(1-34) steadily augmented the contralateral intact tibia BMC (20 days and 40 days: 60 microg of PTH (1-34)/kg/day 9% and 19%, respectively; 200 microg of PTH (1-34)/kg/day 12% and 27%, respectively) and bone mineral density (20 days and 40 days: 60 microg of PTH(1-34)/kg/day 11% and 12%, respectively; 200 microg of PTH(1-34)/kg/day 11% and 15%, respectively).

Dynamic knee loads during gait predict proximal tibial bone distribution

This study tested the validity of the prediction of dynamic knee loads based on gait measurements. The relationship between the predicted loads at the knee and the distribution of bone between the medial and lateral sides of the tibia was examined. The motion and external forces and moments at the knee were measured during gait and a statically determinate muscle model was used to predict the corresponding forces on the medial and lateral tibial plateaus. In particular, the relationship between the knee adduction moment during gait and the ratio or distribution of medial to lateral tibial bone mineral content was studied. Bone mineral content was measured with dual energy X-ray absorptiometry in four regions, two proximal regions 20 mm in height, one medial and one lateral and two distal regions 20 mm in height, one medial and one lateral. The best single predictor of the medial–lateral ratio of proximal bone mineral content (bone distribution) was the adduction moment ( R 2=0.31, p=0.003 ). Adding weight (negative coefficient, p=0.0004) and the ratio of the average predicted peak force on the medial plateau to the predicted peak force on the lateral plateau (positive coefficient, p=0.0033) to the regression model significantly increased the ability to predict the proximal medial–lateral bone distribution ( R 2=0.72, p=0.0001 ). Distally neither the subject characteristics nor the gait moments and predicted forces were significant predictors of the bone distribution. The lack of a correlation distally may be reflective of the forces being more evenly distributed further from the tibial plateau. While it has long been suggested that the adduction moment is the primary determinate of the distribution of load between the medial and lateral plateaus, this is the first evidence of its relationship to the underlying bone distribution.

Altered load history affects periprosthetic bone loss following cementless total hip arthroplasty

Dual energy x-ray absorptiometry was used to measure periprosthetic, distal femoral, and proximal tibial bone mass in the affected and contralateral limbs of eight patients 10 years after unilateral total hip arthroplasty with a cementless, porous-coated titanium alloy femoral stem. Gait analyses to assess the presence of asymmetries in loading of the lower extremities were also performed 10 years postoperatively. The patients had excellent clinical results and no other significant lower extremity pathology. On the basis of comparison of the affected and unaffected proximal femora, bone loss adjacent to the proximal medial aspect of the femoral stem was determined to be 34% (p < 0.001). However, the patients also had 16% less bone in the ipsilateral proximal tibia (p = 0.003) and 15% less bone in the ipsilateral femur 3 cm distal to the prosthesis (p = 0.007) compared with the contralateral limb. When normalized to the asymmetry in tibial bone mineral content, the estimated proximal medial periprosthetic bone loss was still statistically significant, but the magnitude was reduced from 34 to 17% (p = 0.009). The gait analyses indicated that several measures that influence the loads at the hip and knee joints were reduced in the involved limb compared with the contralateral limb. Furthermore, the bilateral difference in the vertical component of the external force acting on the proximal tibia was correlated with the bilateral difference in tibial bone mineral content (r = 0.80, p = 0.02). These data suggest that two mechanical factors, the local stress-shielding effect of the prosthesis and the global effect of decreased loading of the limb, can both make significant contributions to periprosthetic bone loss. It is apparent that the magnitude of the periprosthetic bone loss related to stress-shielding has been overestimated by as much as 50% in retrospective studies.

Unilateral hip replacement causes bilateral changes in tibial bone mineral content in a canine model.

The presence of asymmetry in tibial bone mineral content (BMC) of the operated and control limbs at the end of the experimental period following unilateral hip replacement surgery is used as a marker of limb function. The goal of the present study was to determine the contribution of ipsilateral and contralateral bone gain and loss to control-treated side differences in BMC of the tibia in dogs following unilateral hip replacement surgery. Seven animals were followed longitudinally with single beam photon absorptiometry for 6 months after unilateral hip hemiarthroplasty. Bone loss, compared with preoperative baseline values, was observed in both limbs, with recovery in bone mass beginning 1 month after surgery in the contralateral tibia and 3 months after surgery in the ipsilateral tibia. Thus, the asymmetry in tibial BMC frequently seen after unilateral experimental hip replacement in the canine appears to be caused by differential timing of recovery of bone mass following a transient loss in both limbs. The mechanism defined in this study is in contrast to an alternative mechanism involving bone loss in the treated limb coupled with bone gain in the control limb.

Bone mass at lumbar spine and tibia in young males—impact of physical fitness, exercise, and anthropometric parameters: A prospective study in a cohort of military recruits

Bone mineral density (BMD) and bone mineral content (BMC) were measured using DXA at lumbar spine and tibial diaphyses at the beginning and at the end of a 15-week training period in 151 military recruits of the Swiss army belonging to 5 different troop categories (infantry grenadiers, tank drivers, tank gunners, signalmen, and privates) who each were exposed to physical training of various intensity. At baseline, height, body mass index, and degree of physical fitness independently correlated with vertebral and tibial BMD. Over the 15 weeks of physical training BMD at tibial diaphyses increased by 2.2 +/- 0.3% at the left leg (p = 0.0001) and by 1.1% at the right leg (p = 0.002) with differences between troop categories. At lumbar spine, BMD decreased significantly in tank drivers (-1.2 +/- 0.4%, p = 0.001) and particularly in infantry grenadiers (-2.1 +/- 0.4%) who had the most strenuous weight-bearing training, but not in other troop categories. This decrease was twice as large at the center of the vertebra than for the whole vertebra. These BMD changes were associated with increments in serum levels of osteocalcin and alkaline phosphatase activity. From the initial cohort, 48 subjects volunteered for a third investigation carried out 2 years after the end of the military training period. At this time, lumbar BMD and BMC had risen back to baseline, whereas at tibial diaphyses bone width and BMC but not BMD increased by 5.8 +/- 1.1% and 6.2 +/- 0.9%, respectively, vs. baseline (p = 0.0001 for both).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of treadmill exercise on vertebral and tibial bone mineral content and bone mineral density in the aged adult rat: Determined by dual energy X-ray absorptiometry

Dual energy X-ray absorptiometry (DXA; Hologic QDR-1000W) in an ultrahigh-resolution mode, was used to examine the changes in tibial/fibula and vertebral L4 + L5 bone mineral content (BMC) and bone mineral density (BMD) in each 14-month-old female rat at 0, 9, and 16 weeks of study. Twenty rats were randomized by a stratified weight method into two groups, control and exercised. Exercise consisted of running on a flat-bed treadmill, 17 m/minute, 1 hour/day and 5 days/week. As compared with the control group, a significant increase in tibia/fibula BMC and vertebral BMD was apparent at 9 weeks after exercise training (P = 0.014 by 2-way analysis of variance). The slope of the gain of the tibia/fibula BMC and BMD by 16 weeks of training was ninefold and fivefold higher than that of the control group (P < 0.01 and P < 0.05, respectively, by Mann-Whitney test). The correlation coefficient (r) between the final dry weight of excised bone and the final BMC of the intact rat was 0.843 and 0.71 for tibia/fibula and vertebrae, respectively. In summary, we found that in the aged rat, by 9 weeks, exercise increases BMC and BMD in the tibia, whereas in the vertebrae, only increases in the BMD were found. This study demonstrates that this precise and accurate DXA technique is useful in a longitudinal study of in vivo bone mineral changes in the rat over time by taking into account the individual variation between animals as well as changes between groups.

Changes in tibial bone mass after primary cementless and revision cementless total hip arthroplasty in canine models

The purpose of this study was to examine right-left differences in tibial bone mass after unilateral (left) cementless total hip arthroplasty (THA). Of 39 dogs with THAs, 9 had primary cementless porous-coated femoral stems for 6 months and 15 had similar stems for 2 years. Five dogs had aseptically failed cemented hips, and 10 had aseptically failed cemented hips that were revised with cementless porous-coated femoral stems (5 without bone graft and 5 with autogenous bone graft). These animals were sacrificed 6 months after the revision surgery. The primary cementless dogs showed no right-left difference in tibial bone mineral content (BMC) or cortical bone cross-sectional geometry after 6 months, but after 2 years there was a distal right-left difference in BMC of 6% caused by expansion of the medullary canal in the tibia of the operated limb. Tibial BMC was more than 20% lower in the operated limb of the failed cemented dogs, approximately 15% lower in the nongrafted group, and 7% lower in the grafted group. The right-left tibial difference in BMC in the 2-year primary cementless group is most probably because of subclinical disuse of the operated limb. Among the dogs with failed cemented stems, the lower right-left difference in the two revised groups compared with the non-revised group suggests that improved limb function after cementless revision THA may cause gain of previously lost bone.

Dual photon absorptiometry of the proximal tibia

Bone mineral content (BMC) and bone mineral density (BMD) of the proximal tibia were determined by dual photon absorptiometry on 44 women, aged 23-87 years. The area of the tibia measured was a 2.01 cm region immediately distal to the medial and lateral tuberosities. Values of BMC ranged between 5.09 and 14.57 g and BMD between 0.380 and 1.180 g/cm2. Both tibial BMC and BMD declined with age and tibial BMD was significantly correlated with lumbar spine (r = 0.70), femoral neck (r = 0.73), and femoral trochanter (r = 0.74). However, the large standard errors of estimate (SEE) (0.08-0.14 g/cm2) do not allow for reliable prediction in an individual of other skeletal sites by the tibia. Repeated measurements demonstrated that dual photon absorptiometry of the proximal tibia is a reliable measurement and may be a useful tool in the monitoring of therapeutic or intervention modalities in those individuals with skeletal diseases in whom measurement of the lumbar spine or proximal femur may not be possible.