Biomedical subjects

D M Cullen

Publications and source records attributed to D M Cullen.

At least 19 recordsLinked to original sources

PubMed2003

Effects of nicotine on bone mass and strength in aged female rats.

This study investigated the effects of nicotine on bone mass and biomechanical properties in aged, estrogen-replete (sham-operated) and estrogen-deplete (ovariectomized) female rats. Eight month old, retired breeder, sham-operated and ovariectomized Sprague-Dawley rats were left untreated for 12 weeks to establish cancellous osteopenia in the ovariectomized group. The animals were then administered saline, low dose nicotine (6.0 mg/kg/day) or high dose nicotine (9.0 mg/kg/day) via osmotic minipumps for 12 weeks. Vertebrae and femora were collected at necropsy for determination of bone mass and strength. As expected, ovariectomy had a negative effect on most endpoints evaluated. Vertebral body bone mineral content (BMC) and density (BMD) and the structural (ultimate load and yield load) and material (ultimate stress, yield stress, and flexural modulus of elasticity) strength properties were lower in the OVX rats than in the sham-operated rats. Femoral diaphysis BMC, BMD, ultimate load, and flexural modulus were also lower in the OVX rats than in the sham-operated rats. The nicotine doses administered resulted in serum nicotine levels that averaged 1.5-4.5-fold greater than those observed in heavy smokers. Despite the high doses used, nicotine had no effect on vertebral BMC, BMD, or any of the structural and material strength properties in either the OVX or the Sham rats. In addition, nicotine had no effect on femoral diaphysis BMC, BMD, ultimate load, stiffness, ultimate stress, or flexural modulus. Femoral yield load and stress were lower in low dose nicotine-treated rats than in vehicle-treated rats. However, differences were not detected between the high dose nicotine- and vehicle-treated rats for either femoral yield load or stress. The results suggest that tobacco agents other than nicotine are responsible for the decreased bone density and increased fracture risk as observed in smokers.

Aging↗

PubMed2002

(68)(28)Ni(40): Magicity versus superfluidity.

The neutron-rich (66,68)Ni have been produced at GANIL via interactions of a 65.9A MeV 70Zn beam with a 58Ni target. Their reduced transition probability B(E2;0(+)(1)-->2+) has been measured for the first time by Coulomb excitation in a (208)Pb target at intermediate energy. The B(E2) value for (68)Ni(40) is unexpectedly small. An analysis in terms of large scale shell model calculations stresses the importance of proton core excitations to reproduce the B(E2) values and indicates the erosion of the N = 40 harmonic-oscillator subshell by neutron-pair scattering.

Journal Article↗

PubMed2002

Bone adaptation response to sham and bending stimuli in mice.

This study presents inbred-strain-related differences in tibial bone adaptation response to low-force loading in four-point bending and sham (pad pressure) arrangements in mice. Our previous work in mice has shown that at relatively high but equal bending forces (9 N or a bending moment of 16.88 N-mm), C57BL/6J mice respond with significantly greater bone formation than C3H/HeJ mice. Because of high tibial strains, the majority of the bone response in our previous study was woven bone. In this, study, we reduced the loading forces to 5 N or a bending moment of 9.38 N-mm (to decrease the woven-bone formation response) and investigated inbred-strain-related bone adaptation differences resulting from bending and sham loading (reported here for the first time in C57BL/6J) in these mice. Twenty-four female mice within each inbred mouse strain (C3H/HeJ [C3H] and C57BL/6J [B6]) were randomly divided into the two loading groups (12 per group sham and bending, total of 48 mice). All of the external loading was done for 36 cycles at 2 Hz, 3 d/wk for 3 wk. The bone adaptation response at lower forces exhibited a pattern similar to that seen for the higher forces in the previous study, suggesting that the patterns of bone adaptation were inbred strain related and independent of bending force magnitude. The bending-related periosteal mineral apposition surface (pMS) and mineral apposition rate (MAR) were respectively 40% and 45% greater in B6 than in C3H. The cortical bone adaptation response to bending was greater when compared to sham or pad pressure for each inbred strain of mice, suggesting that the majority of the bone adaptation response was the result of bending stimulus and not local pressure from pad contact. In addition, regardless of loading arrangement (sham or bending), the bone adaptation response in C57BL/6J mice was greater than C3H/HeJ.

Adaptation, Physiological↗

PubMed2001

Effects of nicotine on bone mass, turnover, and strength in adult female rats.

This study investigated the effects of nicotine, the chemical responsible for tobacco addiction, on bone and on serum mineral and calcitropic hormone levels in adult, female rats to help resolve a current controversy regarding the impact of nicotine on bone health. Seven-month-old rats received either saline (n = 12), low-dose nicotine (4.5 mg/kg/day, n = 2), or high-dose nicotine (6.0 mg/kg/day, n = 12) administered subcutaneously via osmotic minipumps for 3 months. Blood, femora, tibiae, and lumbar vertebrae (3-5) were collected at necropsy for determination of serum mineral and hormonal concentrations, bone density (femora and vertebrae), bone turnover (tibiae), and bone strength (femora). The presence of nicotine in serum (111 +/- 7 and 137 +/- 10 ng/ml for the low- and high-dose nicotine groups, respectively) confirmed successful delivery of the drug via osmotic minipumps. Nicotine-induced treatment differences were not detected in serum calcium, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D. However, serum phosphorus and parathyroid hormone (PTH) were higher in rats treated with high-dose nicotine, and serum calcitonin was lower in rats treated with both high- and low-dose nicotine than in control rats. Nicotine treatment had no effect on tibial cancellous or cortical bone turnover or femoral bone mineral content (BMC) and density (BMD). Femoral ultimate load and vertebral BMC were lower in rats treated with high-dose nicotine than in control rats. We conclude that nicotine at serum concentrations 2.5-fold greater than the average in smokers has limited detrimental effects on bone in normal, healthy female rats.

Absorptiometry, Photon↗

PubMed2001

Linear polarization measurement of interband transitions in superdeformed 190hg: model-independent evidence for octupole vibrational structures.

The linear polarization of gamma rays between excited and yrast superdeformed (SD) states in 190Hg was measured using the four-element CLOVER detectors of the EUROBALL IV gamma-ray spectrometer. This measurement shows in a model-independent way that the interband transitions which compete with the highly collective in-band quadrupole transitions are largely enhanced electric dipoles. Not only do these results represent the first measurement of the multipolarity of transitions between different SD states, but they also provide strong evidence for the interpretation of the structures in the SD minimum of the A approximately 190 region in terms of octupole excitations.

Journal Article↗

PubMed2001

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.

Animals↗

PubMed2001

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.

Animals↗

PubMed2001

Bone biomechanical properties in prostaglandin EP1 and EP2 knockout mice.

Prostaglandins play an important role in regulating the bone adaptation response to mechanical stimuli. Prostaglandin E2 (PGE2) is an effective modulator of bone metabolism. Administration of PGE2 to rodents results in increased cancellous and cortical bone mass translating into enhanced mechanical strength. The PGE2 influence on bone is mediated through four well-characterized receptors (EP1, EP2, EP3, and EP4). Although the PGE2 pathways and mechanisms of action on cells involved in bone adaptation are still under investigation, it is now known that each receptor plays a unique role in regulating PGE2-related bone cell function. The EP1 subtype is coupled with Ca2+ mobilization. The EP2 subtype stimulates cyclic adenosine monophosphate (cAMP) formation. cAMP in turn is responsible for the early cellular signal that stimulates bone formation. This study compared physical and biomechanical properties of bone in EP1 and EP2 knockout mice to their corresponding wild-type controls. Ash weight was measured in the ulnae, and femurs and vertebral bodies were tested in three-point bending and compression, respectively. The results suggest: (a) EP1 receptors have a minimal influence on skeletal strength or size in mice; and (b) EP2 receptors have a major influence on the biomechanical properties of bone in mice. The absence of EP2 receptors resulted in weak bone biomechanical strength properties in the EP2 knockout model as compared with the corresponding wild-type control mice.

Animals↗

PubMed2001

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.

Animals↗

PubMed2001

Bone-loading response varies with strain magnitude and cycle number.

Mechanical loading stimulates bone formation and regulates bone size, shape, and strength. It is recognized that strain magnitude, strain rate, and frequency are variables that explain bone stimulation. Early loading studies have shown that a low number (36) of cycles/day (cyc) induced maximal bone formation when strains were high (2,000 microepsilon) (Rubin CT and Lanyon LE. J Bone Joint Surg Am 66: 397-402, 1984). This study examines whether cycle number directly affects the bone response to loading and whether cycle number for activation of formation varies with load magnitude at low frequency. The adult rat tibiae were loaded in four-point bending at 25 (-800 microepsilon) or 30 N (-1,000 microepsilon) for 0, 40, 120, or 400 cyc at 2 Hz for 3 wk. Differences in periosteal and endocortical formation were examined by histomorphometry. Loading did not stimulate bone formation at 40 cyc. Compared with control tibiae, tibiae loaded at -800 microepsilon showed 2.8-fold greater periosteal bone formation rate at 400 cyc but no differences in endocortical formation. Tibiae loaded at -1,000 microepsilon and 120 or 400 cyc had 8- to 10-fold greater periosteal formation rate, 2- to 3-fold greater formation surface, and 1-fold greater endocortical formation surface than control. As applied load or strain magnitude decreased, the number of cyc required for activation of formation increased. We conclude that, at constant frequency, the number of cyc required to activate formation is dependent on strain and that, as number of cyc increases, the bone response increases.

Animals↗

PubMed2000

Genetic variations in bone density, histomorphometry, and strength in mice.

The purpose of this study was to assess breed-related differences in bone histomorphometry, bone biomechanics, and serum biochemistry in three mouse breeds shown to differ in bone mineral density (BMD) (as measured by DXA) and bone mineral content (BMC). Femurs, tibiae, and sera were collected from 16-week-old C3H/HeJ C3H, C57BL/6J BL6, and DBA/2J DBAmice (n = 12/breed). Data collected included BMC and BMD (femora), histomorphometry of cancellous (distal femur) and cortical bone (diaphyseal tibiae and femora), bone strength (femora), and serum alkaline phosphatase (ALP). Consistent with previous reports, BMC and BMD were higher in C3H than in BL6 or DBA mice. The higher BMD in the C3H breed was associated with greater cancellous bone volume, cortical bone area, periosteal bone formation rate, biomechanical strength, and serum ALP. However, mid-diaphyseal total femoral and tibial cross-sectional area and moment of inertia were greatest in BL6, intermediate in C3H, and lowest in DBA mice. The specific distribution of cortical bone in C3H, BL6, DBA mice represents a difference in adaptive response to similar mechanical loads in these breeds. This difference in adaptive response may be intrinsic to the adaptive mechanism, or may be intrinsic to the bone tissue material properties. In either case, the bone-adaptive response to ordinary mechanical loads in the BL6 mice yields bones of lower mechanical efficiency (less stiffness per unit mass of bone tissue) and does not adapt as well as that of the C3H mice where the final product is a bone with greater resistance to bending under load. We suggest that the size, shape, and BMD of the bone are a result of breed-specific genetically regulated cellular mechanisms. Compared with the C3H mice, the lower BMD in BL6 mice is associated with long bones that are weaker because the larger cross-sectional area fails to compensate completely for their lower BMD and BMC.

Absorptiometry, Photon↗

PubMed2000

Effects of nicotine on bone and calciotropic hormones in growing female rats.

Limited research in young adults and immature animals suggests a detrimental effect of tobacco on bone during growth. This study investigated the effects of nicotine, the major alkaloid component of tobacco, on calciotropic hormone concentrations and bone status in growing female rats. One-month-old animals received either saline (n = 10), nicotine at 3.0 mg/kg/day (n = 10), or nicotine at 4.5 mg/kg/day (n = 10) administered subcutaneously via osmotic minipumps for either 2 or 3 months. Sera, femora, tibiae, and lumbar vertebrae (3-5) were collected at necropsy. The concentrations of serum calcium, phosphorus, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, calcitonin, and insulin-like growth factor-I were determined. Bone variables evaluated included mineral content and density (vertebrae and femora), cancellous and cortical histomorphometry (tibiae), and bone strength (vertebrae and femora). Statistically significant differences in serum mineral and hormone concentrations were not associated with nicotine dose or exposure time. No significant nicotine treatment effects were detected for bone mineral content and density, bone histomorphometry, or bone strength. We conclude that nicotine treatment for 2 or 3 months at serum concentrations in the upper range of those found in smokers has no detrimental effect on bone mass, volume, or strength in the growing rat.

Animals↗

PubMed2000

Time course for bone formation with long-term external mechanical loading.

Increased mechanical loading of bone with the rat tibia four-point bending device stimulates bone formation on periosteal and endocortical surfaces. With long-term loading cell activity diminishes, and it has been reported that early gains in bone size may reverse. This study examined the time course for bone cellular and structural response after 6, 12, and 18 wk of loading at 1,200-1, 700 microstrain (muepsilon). Bone formation rates, measured by histomorphometry, were compared within groups, between loaded and contralateral nonloaded tibiae, and between weeks. Formation surface, mineral apposition rate, and bone formation rate on periosteal and endocortical surfaces were elevated after 6 wk of loading. By 12 wk of loading, periosteal and endocortical formation surface and endocortical mineral apposition rates were elevated. By 18 wk of loading, periosteal adaptation appeared complete, whereas endocortical mineral apposition rate remained elevated. No periosteal resorption was observed. Average thickness of new bone formed, from baseline to collection, was greater in loaded than nonloaded tibiae by week 6 and was maintained through week 18. Early increases in bone formation result in periosteal apposition of new bone that persists after formation ceases.

Adaptation, Physiological↗

PubMed1999

Bone response to in vivo mechanical loading in C3H/HeJ mice.

Bone, being sensitive to mechanical stimulus, adapts to mechanical loads in response to bending or deformation. Although the signal/receptor mechanism for bone adaptation to deformation is still under investigation, the mechanical signal is related to the amount of bone deformation or strain. Adaptation to changes in physical activity depends on both the magnitude of increase in strain above average daily levels for maintaining current bone density and the Minimum Effective Strain (MES) for initiating adaptive bone formation. Given the variation of peak bone density that exists in any human population, it is likely that variation in levels for MES is, to a considerable degree, inherited and varies among animal species and breeds. This study showed a dose-related periosteal response to loading in C3H/HeJ mice. The extent of active formation surface, the rate of periosteal bone formation, and area of bone formation increased with increasing peak periosteal strain. In these mice, the loaded tibia consistently showed lower endocortical formation surface and mineral apposition rate than the nonloaded bones at every load level. Although periosteal expansion is the most efficient means of increasing moment of inertia in adaptation to bending, a dose response increase in endocortical formation would have been predicted. Our characterization of the mouse bone formation response to increasing bending loads will be useful in the design of experiments to study the tibial adaptive response to known loads in different mouse breeds.

Animals↗

PubMed1999

Long-term effects of nicotine on bone and calciotropic hormones in adult female rats.

This study determined the effects of nicotine on serum concentrations of several calciotropic hormones, and bone formation and resorption end-points in 7 month old, adult female rats. Animals were administered either saline (n= 9/group), low dose nicotine at 3.0 mg/kg/day (n=10/group) or high dose nicotine at 4.5 mg/kg/day (n=11/group) by subcutaneous osmotic minipumps. At the end of a three months treatment period, serum concentrations of calcium, phosphorus, parathyroid hormone, calcitonin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were determined. Femora, tibiae, and lumbar vertebrae (3-5) were collected and bone parameters evaluated included mineral density and content (femora and vertebrae), strength (femora and vertebrae) and histomorphometry (tibiae). Animals given nicotine had significantly lower levels of 25-hydroxyvitamin D than controls [20.8+/-1.4 ng/ml for the low dose group and 20.7+/-1.0 ng/ ml for the high dose group versus 27.6+/-1.3 ng/ml for the control group (mean+/-S.E.M.), P<0.01]. The high dose nicotine group had smaller vertebral areas (5.4+/-0.2 mm2 versus 6.2+/-0.2 mm2, P<0.05) and a lower bone mineral content than the controls (0.024+/-0.001 g versus 0.030+/-0.001 g, P<0.05). Tibial endocortical mineral apposition rate was also significantly lower in the high dose nicotine group than in the control group (1.06+/-0.13 microm/day versus 1.42+/-0.08 microm/day. P<0.05). No significant treatment differences were detected in bone density, cancellous bone histomorphometry, or bone strength. Results from the present study suggest that nicotine administration may adversely affect bone formation and decrease body storage of vitamin D.

Animals↗

PubMed1998

Bone response to in vivo mechanical loading in two breeds of mice.

We investigated the bone response to external loading in C57BL/6J and C3H/HeJ mice, both breeds with low and high bone density, respectively. An in vivo tibial four-point bending device previously used for application of measured external loads in rats was adapted for mice. It delivered a uniform medio-lateral bending moment to the region of the tibia located 1-5.5 mm proximal to the tibio-fibula junction. The right legs of six C57BL/6J [low bone density (LBD)] and C3H/HeJ [high bone density (HBD)] mice were externally loaded in the device for 36 cycles/day at 2 Hz, 6 days/week for 2 weeks at 9.3 +/- 0.9 N force, inducing estimated lateral periosteal surface compressive strains of 5121 +/- 1128 mu epsilon in C3H/HeJ (HBD) mice (n = 6), significantly higher than the estimated 3988 +/- 820 mu epsilon in C57BL/6J mice (n = 6) (mean +/- SD). In addition, C3H/HeJ HBD mice (n = 11) were externally sham (pad pressure or no bending) loaded in the device for 36 cycles/day at 2 Hz, 3 days/week for 3 weeks at 9.3 +/- 0.9 N force. Calcein injections for bone labeling were given at the 10th and 3rd days before sacrifice. At the end of the experiment, all mice were killed and both tibiae were removed, fixed, embedded, and cross-sectioned through the loaded region. Both tibiae were measured for marrow area (Ma.Ar), cortical area (Ct.Ar), total area (Tt.Ar), cross-sectional moment of inertia (CSMI), and periosteal and endocortical woven bone surface (Wo.B/BS), single-labeled surface (sLS), double-labeled surface (dLS), and total formation surface (FS/BS). Differences in all variables due to breed and loading (both bending and sham-bending) were tested by two-way analysis of variance (ANOVA) (P < 0.05). Ma.Ar, Tt.Ar, and CSMI were greater in C57BL/6J (LBD) than in C3H/HeJ (HBD) mice. Periosteal and endocortical woven bone and formation surface were increased significantly more by loading (bending) in C57BL/6J than in C3H/HeJ mice. Periosteal woven bone response due to sham-bending or sham-loading was significantly lower than due to bending loads in the C3H/HeJ mice. We conclude that the bone response to external loading is greater in LBD mice than in HBD mice. The high bone density of C3H/HeJ (HBD) mice is related to breed-specific factors other than the response to loading.

Analysis of Variance↗

PubMed1998

Time course of osteoblast appearance after in vivo mechanical loading.

The time course of the bone cellular response to mechanical loading is important in the design of optimal exercise prescriptions. This study examined the time course of periosteal cellular changes in the rat tibia following a single exposure of mechanical loading in four-point bending. The right tibiae of adult female Sprague Dawley rats (n = 48, 346 +/- 29 g) were loaded at 40 N (2000 mu epsilon) for 36 cycles at 2 Hz. Right loaded (L) and left nonloaded (NL) tibiae were collected on days 1, 2, 3, 4, 6, and 9 after loading. Cross sections from the loaded region were examined for periosteal differences in bone lining cell surface length, osteoblast surface length, and both alkaline phosphatase-positive cell surface length and width in the cellular layer. A single loading session increased osteoblast surface length as early as day 2, with a peak in expression on day 3. Nine days after a single loading session osteoblast surface length was not different from nonloaded control levels. Alkaline phosphatase width in the cellular periosteum was elevated by day 2 and remained elevated through day 9. This study shows the transient increase in osteoblast surface following a single loading session. It provides fundamental information regarding the timing of osteoblast appearance and the longevity of the response following mechanical stimulation.

Alkaline Phosphatase↗

PubMed1997

Prostaglandin E2 increases the skeletal response to mechanical loading.

The study tested the influence of prostaglandin E2 (PGE2) on the skeletal response to increased in vivo mechanical loading through a four-point bending device. One hundred and twenty Sprague-Dawley female rats (6 months old, 354 +/- 34 g) were divided into 12 groups to accommodate all possible combinations of doses of loads (25, 30, or 35 N) and PGE2 (0, 0.1, 0.3, or 1 mg/kg). Rats received subcutaneous injections of PGE2 daily and in vivo loading of the right tibia every Monday, Wednesday, and Friday for four weeks. Histomorphometric analysis of the periosteal and endocortical surfaces following in vivo dual fluorochrome labeling was performed on both the loaded region of the right tibial diaphysis and a similar region of the left tibial diaphysis. Without PGE2, the threshold for loading to stimulate bone formation was 30 N (peak strain 1360 mu epsilon) at the periosteal surface and 25 N (peak strain 580 mu epsilon) at the endocortical surface. Without loading, the minimum dose of PGE2 to stimulate bone formation at all surfaces was 1 mg/kg/day. When 1 mg/kg/day PGE2 was combined with the minimum effective load, an additive effect of PGE2 and loading on bone formation was observed at the endocortical surface, but a synergistic effect was noted at the periosteal surface. No combined effect of ineffective doses of loading and PGE2 was found. A synergistic effect at peak strains of approximately 1625 mu epsilon on the periosteal surface could suggest either the involvement of locally produced growth factors or autoregulation of endogenous synthesis of PGE2 by exogenously administered PGE2.

Animals↗