Continuous parathyroid hormone and estrogen administration increases vertebral cancellous bone volume and cortical width in the estrogen-deficient rat.

Generally, it is believed that intermittent administration of parathyroid hormone (PTH) has an anabolic effect on the skeleton, whereas continuous administration is catabolic. However, there is evidence that continuous exposure to PTH may have an anabolic effect, for example, in patients with mild primary hyperparathyroidism (PHPT). The possibility of delivering PTH continuously may have important implications for the treatment of osteoporosis. Furthermore, estrogen treatment may be useful in the medical management of PHPT. Therefore, we examined the skeletal effects of continuous administration of PTH, with or without estrogen, in the estrogen-deficient rat with established osteopenia. Forty 7-month-old SD rats were divided into four ovariectomy (OVX) groups and one sham-operated group. Eight weeks post-OVX, three groups received subcutaneous implants of Alzet mini pumps loaded with PTH(1-34) (30 microg/kg per day), 17beta-estradiol (10 microg/kg per day) pellet, or both PTH and 17beta-estradiol separately for 4 weeks. OVX and sham control groups were given the mini pumps loaded with vehicle. Two doses of calcein (10 mg/kg) were given subcutaneously to all rats 2 days and 8 days before death. Histomorphometry was performed on cancellous and cortical bone of the fourth lumbar vertebra. At 3 months, post-OVX rats displayed bone loss with high bone turnover. Estrogen reversed OVX-mediated high turnover without restoring cancellous bone volume (BV/TV). PTH infusion further increased bone turnover and partially restored BV/TV. However, PTH infusion increased cortical porosity. Estrogen inhibited PTH-mediated cancellous bone resorption and substantially increased BV/TV above sham control. The combined treatment was associated with a significant increase in peritrabecular fibrosis and woven bone formation. The combined treatment of PTH infusion and estrogen replacement enhanced cortical width but estrogen did not prevent the PTH-induced cortical tunneling. We conclude that continuous administration of PTH and estrogen increases cortical porosity but has substantial beneficial effects on vertebral cancellous bone volume and cortical width in OVX rats.     

Anabolic action of parathyroid hormone (PTH) does not compromise bone matrix mineral composition or maturation

Intermittent administration of parathyroid hormone (PTH) is used to stimulate bone formation in patients with osteoporosis. A reduction in the degree of matrix mineralisation has been reported during treatment, which may reflect either production of undermineralised matrix or a greater proportion of new matrix within the bone samples assessed. To explore these alternatives, high resolution synchrotron-based Fourier Transform Infrared Microspectroscopy (sFTIRM) coupled with calcein labelling was used in a region of non-remodelling cortical bone to determine bone composition during anabolic PTH treatment compared with region-matched samples from controls.8 week old male C57BL/6 mice were treated with vehicle or 50 μg/kg PTH, 5 times/week for 4 weeks (n = 7–9/group). Histomorphometry confirmed greater trabecular and periosteal bone formation and 3-point bending tests confirmed greater femoral strength in PTH-treated mice. Dual calcein labels were used to match bone regions by time-since-mineralisation (bone age) and composition was measured by sFTIRM in six 15 μm² regions at increasing depth perpendicular to the most immature bone on the medial periosteal edge; this allowed in situ measurement of progressive changes in bone matrix during its maturation.The sFTIRM method was validated in vehicle-treated bones where the expected progressive increases in mineral:matrix ratio and collagen crosslink type ratio were detected with increasing bone maturity. We also observed a gradual increase in carbonate content that strongly correlated with an increase in longitudinal stretch of the collagen triple helix (amide I:amide II ratio). PTH treatment did not alter the progressive changes in any of these parameters from the periosteal edge through to the more mature bone.These data provide new information about how the bone matrix matures in situ and confirm that bone deposited during PTH treatment undergoes normal collagen maturation and normal mineral accrual.     

BMP signaling is required for adult skeletal homeostasis and mediates bone anabolic action of parathyroid hormone

Bmp2 and Bmp4 genes were ablated in adult mice (KO) using a conditional gene knockout technology. Bones were evaluated by microcomputed tomography (μCT), bone strength tester, histomorphometry and serum biochemical markers of bone turnover. Drill-hole was made at femur metaphysis and bone regeneration in the hole site was measured by calcein binding and μCT. Mice were either sham operated (ovary intact) or ovariectomized (OVX), and treated with human parathyroid hormone (PTH), 17β-estradiol (E2) or vehicle. KO mice displayed trabecular bone loss, diminished osteoid formation and reduced biomechanical strength compared with control (expressing Bmp2 and Bmp4). Both osteoblast and osteoclast functions were impaired in KO mice. Bone histomorphomtery and serum parameters established a low turnover bone loss in KO mice. Bone regeneration at the drill-hole site in KO mice was lower than control. However, deletion of Bmp2 gene alone had no effect on skeleton, an outcome similar to that reported previously for deletion of Bmp4 gene. Both PTH and E2 resulted in skeletal preservation in control-OVX, whereas in KO-OVX, E2 but not PTH was effective which suggested that the skeletal action of PTH required Bmp ligands but E2 did not. To determine cellular effects of Bmp2 and Bmp4, we used bone marrow stromal cells in which PTH but not E2 stimulated both Bmp2 and Bmp4 synthesis leading to increased Smad1/5 phosphorylation. Taken together, we conclude that Bmp2 and Bmp4 are essential for maintaining adult skeletal homeostasis and mediating the anabolic action of PTH.     

Recombinant human parathyroid hormone (1-34) [teriparatide] improves both cortical and cancellous bone structure.

Histomorphometry and microCT of 51 paired iliac crest biopsy specimens from women treated with teriparatide revealed significant increases in cancellous bone volume, cancellous bone connectivity density, cancellous bone plate-like structure, and cortical thickness, and a reduction in marrow star volume. INTRODUCTION: We studied the ability of teriparatide (rDNA origin) injection [rhPTH(1-34), TPTD] to improve both cancellous and cortical bone in a subset of women enrolled in the Fracture Prevention Trial of postmenopausal women with osteoporosis after a mean treatment time of 19 months. This is the first report of a biopsy study after treatment with teriparatide having a sufficient number of paired biopsy samples to provide quantitative structural data. METHODS: Fifty-one paired iliac crest bone biopsy specimens (placebo [n = 19], 20 microg teriparatide [n = 18], and 40 microg teriparatide [n = 14]) were analyzed using both two-dimensional (2D) histomorphometry and three-dimensional (3D) microcomputed tomography (microCT). Data for both teriparatide treatment groups were pooled for analysis. RESULTS AND CONCLUSIONS: By 2D histomorphometric analyses, teriparatide significantly increased cancellous bone volume (median percent change: teriparatide, 14%; placebo, -24%; p = 0.001) and reduced marrow star volume (teriparatide, -16%; placebo, 112%; p = 0.004). Teriparatide administration was not associated with osteomalacia or woven bone, and there were no significant changes in mineral appositional rate or wall thickness. By 3D cancellous and cortical bone structural analyses, teriparatide significantly decreased the cancellous structure model index (teriparatide, -12%; placebo, 7%; p = 0.025), increased cancellous connectivity density (teriparatide, 19%; placebo, - 14%; p = 0.034), and increased cortical thickness (teriparatide, 22%; placebo, 3%; p = 0.012). These data show that teriparatide treatment of postmenopausal women with osteoporosis significantly increased cancellous bone volume and connectivity, improved trabecular morphology with a shift toward a more plate-like structure, and increased cortical bone thickness. These changes in cancellous and cortical bone morphology should improve biomechanical competence and are consistent with the substantially reduced incidences of vertebral and nonvertebral fractures during administration of teriparatide.     

Canine cortical bone autograft remodeling in two simultaneous skeletal sites

The morphological and physical aspects of cortical bone autografts implanted in dogs for 1-9 months in two differently located skeletal defects are reported with a twofold aim: to provide a reference system for further comparison with various allografts and to delineate a general pattern of cortical bone graft healing. A 3-cm osteoperiosteal gap was created in the diaphyseal segment of the ulna and fibula of mature dogs. The grafts, freed from periosteum and bone marrow, were then inverted and replaced for the autografts in the left limb bone without internal fixation or external splints. On the right side, different allografts were tested. A group of three animals also had an unfilled segmental resection on the right as control. Dogs were observed for 1, 2, 3, 6, and 9 months and were able to bear weight within 3 days. Twenty-eight ulnae and 27 fibulae were available for this autograft study. Fluorochromes were injected at mid-term and at the end of the observation. All the grafts were assessed morphologically by cross-section microradiographs and ultraviolet light microscopy, and a morphometric analysis for porosity and fluorescence was done. To evaluate the physical aspects of graft healing, the recovered ulnar autografts, when available, were submitted to photon absorptiometry and to torsional loading. Morphologically, resorption was found to invade the cortical bone graft transversely through radial tunnels, and in addition to the host-bone-graft junction, the entire transplant surface provided another way for revascularization. The highest porosity level was achieved 2 months after surgery for both ulna and fibula, while new bone formation, as assessed by fluorochromes, was most important at 3 months. At 9 months, porosity remained above the normal range as determined in a set of five nongrafted dogs. While the lack of correlation for porosity between the two grafts suggests that local factors are more important in graft resorption, the observed correlation for fluorescence indicates that new bone deposition is more dependent upon skeletal metabolic activity. Within each graft, porosity and new bone formation were not well correlated. In the ulna, the bone mineral content (BMC) reflected the graft volumetric variations during the remodeling, with the lowest mean value at 3 months. For each graft, BMC was well correlated with the torsional stiffness. When torsionally loaded, the maximal tangential shear stress at failure of the graft was negatively related to its cortical porosity.(ABSTRACT TRUNCATED AT 400 WORDS)     

Canine cortical bone autograft remodeling in two simultaneous skeletal sites

Summary The morphological and physical aspects of cortical bone autografts implanted in dogs for 1–9 months in two differently located skeletal defects are reported with a twofold aim: to provide a reference system for further comparison with various allografts and to delineate a general pattern of cortical bone graft healing. A 3-cm osteoperiosteal gap was created in the diaphyseal segment of the ulna and fibula of mature dogs. The grafts, freed from periosteum and bone marrow, were then inverted and replaced for the autografts in the left limb hone without internal fixation or external splints. On the right side, different allografts were tested. A group of three animals also had an unfilled segmental resection on the right as control. Dogs were observed for 1, 2, 3, 6, and 9 months and were able to bear weight within 3 days. Twenty-eight ulnae and 27 fibulae were available for this autograft study. Fluorochromes were injected at mid-term and at the end of the observation. All the grafts were assessed morphologically by cross-section microradiographs and ultraviolet light microscopy, and a morphometric analysis for porosity and fluorescence was done. To evaluate the physical aspects of graft healing, the recovered ulnar autografts, when available, were submitted to photon absorptiometry and to torsional loading. Morphologically, resorption was found to invade the cortical bone graft transversely through radial tunnels, and in addition to the host-bone-graft junction, the entire transplant surface provided another way for revascularization. The highest porosity level was achieved 2 months after surgery for both ulna and fibula, while new bone formation, as assessed by fluorochromes, was most important at 3 months. At 9 months, porosity remained above the normal range as determined in a set of five nongrafted dogs. While the lack of correlation for porosity between the two grafts suggests that local factors are more important in graft resorption, the observed correlation for fluorescence indicates that new bone deposition is more dependent upon skeletal metabolic activity. Within each graft, porosity and new bone formation were not well correlated. In the ulna, the bone mineral content (BMC) reflected the graft volumetric variations during the remodeling, with the lowest mean value at 3 months. For each graft, BMC was well correlated with the torsional stiffness. When torsionally loaded, the maximal tangential shear stress at failure of the graft was negatively related to its cortical porosity. From this study, it appears that resorption and new bone formation follow the same temporal evolution in two differently located cortical bone autografts when expressed in terms of porosity and fluorescence. Nine months after implantation, the graft healing remains incomplete. Porosity, reflecting the state of intracortical repair, emerges as a critical factor in graft torsional strength.     

Systemic intermittent parathyroid hormone treatment improves osseointegration of press-fit inserted implants in cancellous bone

Background and purpose Intermittent administration of parathyroid hormone (PTH) has an anabolic effect on bone, as confirmed in human osteoporosis studies, distraction osteogenesis, and fracture healing. PTH in rat models leads to improved fixation of implants in low-density bone or screw insertion transcortically. Material and methods We examined the effect of human PTH (1-34) on the cancellous osseointegration of unloaded implants inserted press-fit in intact bone of higher animal species. 20 dogs were randomized to treatment with human PTH (1-34), 5 μg/kg/day subcutaneously, or placebo for 4 weeks starting on the day after insertion of a cylindrical porous coated plasma-sprayed titanium alloy implant in the proximal metaphyseal cancellous bone of tibia. Osseointegration was evaluated by histomorphometry and fixation by push-out test to failure. Results Surface fraction of woven bone at the implant interface was statistically significantly higher in the PTH group by 1.4 fold with (median (interquartile range) 15% (13-18)) in the PTH group and 11% (7-13) in control. The fraction of lamellar bone was unaltered. No significant difference in bone or fibrous tissue was observed in the circumferential regions of 0-500, 500-1,000, and 1,000-2,000 μm around the implant. Mechanically, the implants treated with PTH showed no significant differences in total energy absorption, maximum shear stiffness, or maximum shear strength. Interpretation Intermittent treatment with PTH (1-34) improved histological osseointegration of a prosthesis inserted press-fit at surgery in cancellous bone, with no additional improvement of the initial mechanical fixation at this time point.     

Differential temporal effects of sclerostin antibody and parathyroid hormone on cancellous and cortical bone and quantitative differences in effects on the osteoblast lineage in young intact rats

Sclerostin antibody (Scl-Ab) and parathyroid hormone (PTH) are bone-forming agents that have different modes of action on bone, although a study directly comparing their effects has not been conducted. The present study investigated the comparative quantitative effects of these two bone-forming agents over time on bone at the organ, tissue, and cellular level; specifically, at the level of the osteoblast (Ob) lineage in adolescent male and female rats. Briefly, eight-week old male and female Sprague–Dawley rats were administered either vehicle, Scl-Ab (3 or 50 mg/kg/week subcutaneously), or human PTH (1–34) (75 μg/kg/day subcutaneously) for 4 or 26 weeks. The 50 mg/kg Scl-Ab and the PTH dose were those used in the respective rat lifetime pharmacology studies. Using robust stereological methods, we compared the effects of these agents specifically at the level of the Ob lineage in vertebrae from female rats. Using RUNX2 or nestin immunostaining, location, and morphology, the total number of osteoprogenitor subpopulations, Ob, and lining cells were estimated using the fractionator or proportionator estimators. Density estimates were also calculated referent to total bone surface, total Ob surface, or total marrow volume.Scl-Ab generally effected greater increases in cancellous and cortical bone mass than PTH, correlating with higher bone formation rates (BFR) at 4 weeks in the spine and mid-femur without corresponding increases in bone resorption indices. The increases in vertebral BFR/BS at 4 weeks attenuated with continued treatment to a greater extent with Scl-Ab than with PTH. At 4 weeks, both Scl-Ab and PTH effected equivalent increases in total Ob number (Ob.N). Ob density on the formative surfaces (Ob.N/Ob.S) remained similar across groups while mineral apposition rate (MAR) was significantly higher with Scl-Ab at week 4, reflecting an increase in individual Ob vigor relative to vehicle and PTH. After 26 weeks, Scl-Ab maintained BFR/BS with fewer Ob and lower Ob.N/Ob.S by increasing the Ob footprint (bone surface area occupied by an Ob) and increasing MAR, compared with PTH. The lower Ob.N and Ob.N/Ob.S with Scl-Ab at 26 weeks were associated with decreased osteoprogenitor numbers compared with both vehicle and PTH, an effect not evident at week 4. Osteoprogenitor numbers were generally positively correlated with Ob.N across groups and timepoints, suggesting dynamic coordination between the progenitor and Ob populations. The time-dependent reductions in subpopulations of the Ob lineage with Scl-Ab may be integral to the greater attenuation or self-regulation of bone formation observed at the vertebra, as PTH required more Ob at the formative site with correlative increased numbers of progenitors compared with Scl-Ab indicating potentially greater stimulus for progenitor pool proliferation or differentiation.     

Relationship between bone mass and rates of bone change at appendicular measurement sites.

The rate of bone change among postmenopausal women may vary depending upon the initial bone mass. Examining this possibility is difficult, however, because of a negative statistical bias that occurs when change is regressed against the initial value of the same variable. In this article, four statistical methods were applied to measure the association between bone mass and the rate of bone change. The study population was Japanese-American women, who were monitored for approximately 5 years. Bone changes were determined for the calcaneus and the distal and proximal radius. The results were consistent across the bone sites but differed between statistical methods. Three of the four methods indicated that the women with the greater bone mass had the greater loss rates. The fourth method did not support this association. Possible reasons for the discordant results are discussed. Using the "best" estimate of the relationship, a gradual convergence of bone mass was projected over time toward the population mean. The convergence occurred because women with higher bone mass had a somewhat faster loss rate than women with lower bone mass. Overall, however, the variation in bone mass between individuals was large compared to the rate of convergence.     

Differential effects of glucocorticoids on cortical appendicular and cortical vertebral bone mineral content

Summary The susceptibility to glucocorticoid-induced bone loss may vary in different parts of the skeleton. We studied 62 patients with rheumatoid arthritis, 26 of whom were on low-dose glucocorticoid treatment. Bone mineral content (BMC) in the forearm was measured by single photon absorptiometry at a cortical, diaphyseal, and at a mixed cortical and trabecular, metaphyseal site. Lumbar BMC was measured by dual energy computed tomography in a trabecular and a cortical region of interest. The presence of vertebral deformities was evaluated on lateral spine radiographs. After correction for possibly confounding variables, prednisone therapy significantly influenced BMC at both the trabecular (-22.0%, 95% confidence interval-36.0% to-8.1%) and cortical (-24.8%, 95% confidence interval-39.3% to-10.3%) lumbar site. A significant effect was also seen at the metaphyseal (-15.7%, 95% confidence interval-27.1% to-4.2%), but not the diaphyseal (-3.9%, 95% confidence interval-14.1% to 6.4%) site in the forearm. Correlations between peripheral and vertebral BMC were moderate at best. The diaphyseal to metaphyseal BMC ratio did not identify patients with vertebral osteoporosis. It is concluded that the anterior cortical rim of the vertebral body is more susceptible to the effects of glucocorticoids than the cortical bone in the forearm, and that measurements of trabecular and anterior cortical vertebral BMC are essential in the management of patients with possible glucocorticoid-associated osteoporosis.     

Effects of tobacco use on axial and appendicular bone mineral density

Tobacco use has been identified as being a risk factor for the development of osteoporosis. While some data have suggested an effect on peripheral bone mass there are little previous data examining the role of tobacco use in axial skeletal bone loss. We examined tobacco use in relation to lumbar spine and proximal femur bone mineral density and forearm bone mineral content in 203 women. Data from identical twin pairs, comprising a subgroup of the larger group as well as a small number of male twin pairs, was also analyzed. The data show a difference in lumbar and proximal femur BMD of 0.03 and 0.06 g/cm2 respectively between smoking and nonsmoking identical twins. There was however no difference in the cross-sectional studies and no significant deleterious effect detected of tobacco use on forearm bone mineral content. The effect of smoking on lumbar and proximal femur bone mineral density, in identical twins discordant for tobacco use, was equivalent on average to 3 to 4 years of normal postmenopausal bone loss.     

Interaction between parathyroid hormone and catecholamines on renal cortical cyclic AMP.

Parathyroid hormone (PTH) and catecholamines (CA) increased cAMP levels in isolated tubules of rat renal cortex. A rise in cAMP could be detected 10 sec after the addition of agonists, and it reached the peak in 30-60 sec and then decreased despite the presence of active agonists. Direct relationships exist between theophylline concentrations and cAMP levels in response to agonists. Three- to fivefold rises in cAMP levels were observed with a maximal dose of PTH compared with that of CA, and there was no additive effect. Both PTH and CA stimulated renal gluconeogenesis; when added together with each maximal dose, no additive effect was observed. These results suggest the important role of phosphodiesterase to control tubular cAMP in response to hormonal stimuli, and there is a tubule cell group responding to both PTH and CA.     

The influence of combined parathyroid hormone and growth hormone treatment on cortical bone in aged ovariectomized rats.

The influence of combined parathyroid hormone (PTH) and growth hormone (GH) treatment on bone formation and mechanical strength was investigated in femoral middiaphysial cortical bone from 20-month-old ovariectomized (OVX) rats. The animals were OVX at 10 months of age, and at 18 months they were treated daily for 56 days with PTH(1-34) alone (60 microg/kg), recombinant human GH (rhGH) alone (2.7 mg/kg), or a combination of PTH(1-34) plus rhGH. Vehicle was given to OVX control rats. All animals were labeled at day 28 (calcein) and at day 49 (tetracycline) of the treatment period. PTH(1-34) alone gave rise to formation of a new zone of bone at the endocortical surface. rhGH alone caused substantial bone deposition at the periosteal surface without influencing the endocortical surface. Combined PTH(1-34) plus rhGH administration enhanced bone deposition at the periosteal surface to the same extent as that of rhGH alone. However, the combined treatment resulted in a more pronounced formation of new bone at the endocortical surface than was induced by PTH(1-34) alone. Both PTH(1-34) alone and rhGH alone increased the mechanical strength of the femoral diaphysis, and further increase in mechanical strength resulted from combined PTH(1-34) plus rhGH treatment. OVX by itself induced the characteristic increase in medullary cavity cross-sectional area and a minor decrease in the mechanical quality of the osseous tissue.     

Differences in non-enzymatic glycation and collagen cross-links between human cortical and cancellous bone

Summary

It is important to establish the relationship between pentosidine and advanced glycation endproducts (AGEs) in bone. We found the relationship between pentosidine and AGEs and their magnitude of accumulation were dependent on bone’s surface-to-volume ratio. Results illustrate the importance of measuring pentosidine and AGEs separately in cancellous and cortical bone.

Introduction

Accumulation of collagen cross-links (AGEs) produced by non-enzymatic glycation deteriorates bone’s mechanical properties and fracture resistance. Although a single AGE, pentosidine, is commonly used as a representative marker, it is unclear whether it quantitatively reflects total fluorescent AGEs in bone. The goal of this study was to establish the relationship between pentosidine and total AGEs in cancellous and cortical bone.

Methods

Pentosidine and total AGEs were quantified in 170 human bone samples. Total fluorescent AGEs were measured in 28 additional cancellous and cortical bone specimens of the same apparent volume that were incubated in control or in vitro glycation solutions. Correlations between pentosidine and total AGEs and differences between cortical and cancellous groups were determined.

Results

Pentosidine was correlated with total AGEs in cancellous bone (r?=?0.53, p?<?0.0001) and weakly correlated in cortical bone (r?=?0.23, p?<?0.05). There was more pentosidine (p?<?0.01) and total AGEs (p?<?0.001) in cancellous than in cortical bone. The in vitro glycation substudy showed that cancellous bone accumulated more AGEs than cortical bone (p?<?0.05).

Conclusion

The relationship between pentosidine and total AGEs and their magnitude of accumulation differed in cancellous and cortical bone of the same apparent volume, and were dependent on the surface-to-volume ratios of each sample. It is important to consider the bone types as two separate entities, and it is crucial to quantify total AGEs in addition to pentosidine to allow for more comprehensive analysis of the effects of non-enzymatic glycation in bone.     

Anabolic effects of human biosynthetic parathyroid hormone fragment (1-34), LY333334, on remodeling and mechanical properties of cortical bone in rabbits.

Intermittent administration of parathyroid hormone (PTH) has an anabolic effect in cancellous bone of osteoporotic humans. However, the effect of PTH on cortical bone with Haversian remodeling remains controversial. The aim of this study was to determine the effects of biosynthetic human PTH(1-34) on the histology and mechanical properties of cortical bone in rabbits, which exhibit Haversian remodeling. Mature New Zealand white rabbits were treated with once daily injections of vehicle, or PTH(1-34), LY333334, at 10 micrograms/kg/day or 40 micrograms/kg/day for 140 days. Body weight in rabbits treated with PTH did not change significantly over the experimental period. Serum calcium and phosphate were within the normal range, but a 1 mg/ml increase in serum calcium was observed in rabbits given the higher dose of PTH. Histomorphometry of cortical bone in the midshaft of the tibia showed significant increases in periosteal and endocortical bone formation in these rabbits. Intracortical bone remodeling in the tibia was activated and cortical porosity increased by PTH. Cross-sectional bone area and bone mass of the midshaft of the femur increased significantly after PTH treatment. Ultimate force, stiffness, and work to failure of the midshaft of the femur of rabbits given the 40 micrograms dose of PTH were significantly greater than those in the control group, whereas elastic modulus was significantly lower than that in the rabbits given the 10 micrograms dose of PTH, but not different from controls. In the third lumbar vertebra, PTH increased both formation and resorption without increasing cancellous bone volume. The increases in bone turnover and cortical porosity were accompanied by concurrent increases in bone at the periosteal and endocortical surfaces. The combination of these phenomena resulted in an enhancement of the ultimate stress, stiffness, and work to failure of the femur.     

Comparative effects of intermittent administration of human parathyroid hormone (1-34) on cancellous and cortical bone loss in tail-suspended and sciatic neurectomized young rats

 We compared the effects of intermittent administration of human parathyroid hormone (PTH) (1-34) on tibial cancellous and cortical bone loss in tail-suspended and sciatic neurectomized young rats. Forty-eight 6-week-old male Wistar rats were randomly divided into six groups with eight animals each: age-matched controls (AMC), tail suspension (TS), sciatic neurectomy (NX), AMC + PTH, TS + PTH, and NX + PTH. Fifteen days after the start of the experiment, the proximal tibia and tibial shaft were processed for cancellous and cortical bone histomorphometric analyses, respectively. The reduction of cancellous bone volume (BV/TV) was significantly greater in the TS group than in the NX group, whereas the reduction of percent cortical area (Ct Ar) did not differ significantly between the TS and NX groups. Administration of human PTH to rats in the TS and NX groups increased BV/TV to a level significantly higher than that of the AMC group. Administration of human PTH to rats in the NX group significantly increased percent Ct Ar, but percent Ct Ar of the NX group was still significantly lower than that of the AMC group. Administration of human PTH to rats in the TS group did not significantly affect percent Ct Ar. These findings suggest that intermittent administration of human PTH (1-34) at the dose we used may completely prevent cancellous bone loss both in TS and NX young rats, and that it may not affect cortical bone loss in TS young rats but only attenuate it in NX young rats. Received: October 3, 2001 / Accepted: December 20, 2001