PubMed Health⌕ Search

Biomedical subjects

Nozomu Inoue

Publications and source records attributed to Nozomu Inoue.

At least 19 recordsLinked to original sources
PubMed2006

Intradiscal injections of osteogenic protein-1 restore the viscoelastic properties of degenerated intervertebral discs.

BACKGROUND CONTEXT: Using biochemical, histological, and radiological parameters in a rabbit model of intervertebral disc (IVD) degeneration, the intradiscal injection of a growth factor, such as osteogenic protein-1 (OP-1), has been shown to regenerate the IVD. However, very little is known about how such a biological therapeutic approach affects the biomechanical properties of the degenerated IVD. PURPOSE: To investigate the effects of an intradiscal injection of OP-1 on the biomechanical properties of IVDs in the rabbit annular-puncture disc degeneration model and to determine their relationship to biochemical properties. STUDY DESIGN/SETTING: In vivo study on the effects of intradiscally administered OP-1 on the biomechanical and biochemical properties of IVDs in the rabbit annular-puncture disc degeneration model. METHODS: New Zealand White rabbits (n=16) underwent annulus fibrosus (AF) puncture, using an 18-gauge needle, at L2-L3 and L4-L5 (L3-L4: nonpunctured control). Four weeks later, the punctured discs received an injection of either 5% lactose (10 microL) or OP-1 (100 microg/10 microL of 5% lactose) into the nucleus pulposus (NP). The disc height was radiographically monitored biweekly. After sacrifice and removal of bone-disc-bone complexes 8 weeks postinjection, the dynamic viscoelastic properties of the IVDs were tested by applying a cycle of sinusoidal strain in uniaxial compression at six loading frequencies (0.05 to 2 Hz). The biochemical properties of the dissected IVDs were then analyzed and correlated with the biomechanical properties. RESULTS: A single injection of OP-1 significantly restored disc height when compared with the lactose-injected discs (OP-1 vs. lactose, p<.001). The elastic modulus of the IVDs in the OP-1-injected discs was significantly higher than that in the lactose-injected discs at all frequencies (mean: +43%, p<.001). The viscous modulus in the OP-1-injected discs was significantly higher at 0.05, 0.2, 0.5, and 1 Hz (mean: +55%, p<.001) and showed higher tendencies at other frequencies (p=.08-.09). For both moduli, no significant differences were observed between the OP-1-injected and the nonpunctured control discs. The OP-1 injection significantly increased the proteoglycan (PG) content in the NP and AF, and the collagen content in the NP (p<.001-.05). Both elastic and viscous moduli showed significant positive correlations with PG content in the NP and collagen content in the NP and AF (Rho=.357-.466, p=.010-.047). CONCLUSIONS: We have shown for the first time that an injection of the growth factor, OP-1, restored the biomechanical properties of IVDs in a rabbit model of IVD degeneration. Comparing biomechanical with biochemical data suggests that the OP-1-induced biomechanical restoration was a consequence of increased activities of anabolic pathways that resulted in biochemical changes in the IVD.

Animals↗
PubMed2006

Three-dimensional in vivo measurement of lumbar spine segmental motion.

STUDY DESIGN: Fifteen asymptomatic volunteers were externally rotated and CT scanned to determine lumbar segmental motion. OBJECTIVES: To measure three-dimensional segmental motion in vivo using a noninvasive measurement technique. SUMMARY OF BACKGROUND DATA: Spinal instability has been implicated as a potential cause of low back pain, especially, axial rotational instability. Typically, flexion-extension lateral radiographs were used to quantify instability, but inaccurately measured translations and inability to capture out-of-plane rotations are limitations. METHODS: Using a custom-calibrated rotation jig, L1-S1 CT reconstructions were created of volunteers in each of 3 positions: supine and left and right rotations of the torso with respect to the hips. Segmental motions were calculated using Euler angles and volume merge methods in three major planes. RESULTS: Segmental motions were small (< 4 degrees or 6 mm) with the greatest motions seen in axial rotation (range, 0.6 degrees to 2.2 degrees ), lateral bending (range, -3.6 degrees to 3.0 degrees ), and frontal translation (-1.2 mm to 5.4 mm). Largest motions were in the levels: L1-L2 to L3-L4. CONCLUSIONS: Complex coupled motions were measured due to external torsion and could be indicative of instability chronic patients with low back pain. The presented data provide baseline segmental motions for future comparisons to symptomatic subjects.

Adult↗
PubMed2006

Anti-adhesion properties of a thrombin-based hemostatic gelatin in a canine laminectomy model: a biomechanical, biochemical, and histologic study.

STUDY DESIGN: An in vivo study on the effects of an agent for scar prevention in a dog laminectomy model. OBJECTIVE: To examine the anti-adhesion properties of a thrombin-based hemostatic gelatin (FLOSEAL; Baxter International Inc., Deerfield, IL). SUMMARY OF BACKGROUND DATA: Postlaminectomy dural adhesion sometimes causes symptomatic problems. Although a new type of hemostatic agent, a thrombin-based hemostatic gelatin, has been developed, its effect on postlaminectomy scar prevention is unknown. METHODS: A 4-level lumbar laminectomy was performed on 11 adult mongrel dogs. There were 2 levels randomly chosen to receive the thrombin-based hemostatic gelatin treatment, while the remaining levels were untreated (control). Dogs were euthanized 8 weeks after surgery. To assess the tenacity of adhesion between the dura and scar, peel-off testing was performed. Gross, biochemical, and histologic analyses were then used to examine the samples. RESULTS: Peel-off stiffness was significantly decreased in the treatment group (64.8% of the control, P = 0.032; 2-tailed unpaired t test). Histologically, there was significantly less scar tissue formation in the treatment group (P = 0.04). The gross analyses showed a trend toward a smaller amount of scar tissue and tenacity of adhesion between the dura and scar in the treatment group. Biochemically, there was a trend toward a lower collagen cross-links content in the treatment group (P = 0.07). CONCLUSIONS: The thrombin-based hemostatic gelatin decreases the tenacity of adhesion between the dura and scar at laminectomy sites.

Animals↗
PubMed2005

Tendon reattachment to a metallic implant using an allogenic bone plate augmented with rhOP-1 vs. autogenous cancellous bone and marrow in a canine model.

Functionality of endoprosthetic reconstruction may be improved through secure and lasting soft tissue reattachment directly to the metallic implant surface. Tendon reattachment to the metallic surface of a titanium implant (enhanced tendon anchor, ETA) using autogenous bone plate as an interpositional structure between the tendon and metal, augmented with autogenous bone chips and marrow, provided successful mechanical and functional outcome. However, preparation of the autogenous bone plate is not practical in a clinical setting, but application of an allogenic bone plate could be an alternative. The autogenous cancellous bone and marrow may also be substituted by bone growth factors so that no autogenous bone graft is required. We hypothesized that the reconstitution of the direct tendon-bone insertion morphology in tendon reattachment to metallic implant could be achieved using allogenic cancellous bone plate augmented with autogenous cancellous bone and marrow, and that the autogenous bone grafts could be replaced by recombinant human osteogenic protein-1 (rhOP-1). In two canine groups the supraspinatus tendon was reattached unilaterally to a modified ETA implant with a highly porous metallic surface known as Tritanium Dimensionalized Metal. Allogenic bone plates saturated with rhOP-1-collagen putty were used in the OP-1 (OP) group, while plates saturated with autogenous cancellous bone and marrow were used in the bone marrow (BM) group. Functional, radiographical, mechanical and histomorphological analysis results were compared between both groups. At 15 weeks, gait analysis showed 78% and 81% recovery of preoperative weight-bearing in OP and BM groups, respectively. The calcified area around the tendon in OP group was 5.2 times larger than that in BM group (p<0.001). The ultimate tensile strength of the reattachment was 24% and 38% of the intact contralateral side in OP and BM groups, respectively, without significant difference between them. There was evidence of tendon-bone insertion transitional zones, tissue ingrowth and adhesion to the metallic surface in both groups. In conclusion, the use of the allograft combined with rhOP-1 had a similar effect as combined with autogenous cancellous bone and marrow in the tendon reattachment to the metallic surface.

Animals↗
PubMed2005

The effect of multidrug chemotherapy on bone graft augmented prosthesis fixation.

Use of combination adjuvant chemotherapies have improved the disease free survival rate of tumor patients significantly. However, studies have shown that chemotherapeutic agents have negative effects on bone graft incorporation and fixation of porous-coated prostheses needed for reconstruction of bone defects after wide resection of malignant tumors. Unilateral resection of a 6-cm segment of the femoral diaphysis and reconstruction with a porous-coated segmental prosthesis was performed in eight mixed-breed dogs under perioperative chemotherapy with doxorubicin, cisplatin, and ifosfamide. Eight strips of autogenous cortical bone were evenly placed around the junctions between the femur and the prosthetic surface. Autogenous cancellous bone was placed under and between the strips of cortical bone. Two cycles of the chemotherapy were given preoperatively, and three cycles postoperatively. The animals were followed for 12 weeks, with sequential assessments of weight-bearing and radiographic evaluation. Biomechanical, histological, and microradiographic analyses of the retrieved specimens were performed. Doxorubicin, cisplatin, and ifosfamide combination chemotherapy showed a significant effect on new bone formation as seen in reduced callus size and lower ultimate strength of extracortical fixation. However, the onlay corticocancellous grafting method provided better biologic fixation of the prosthesis compared with fixation without any bone grafting under non-chemotherapy condition in a previous study. Extracortical bone grafting is an effective modality for implant fixation even under intensive chemotherapy.

Animals↗
PubMed2005

Computational simulation of axial dynamization on long bone fractures.

BACKGROUND: Axial dynamization has been shown in previous studies to promote callus formation, improve bone healing at fracture sites, and enhance bone remodeling. However, the possibility of non-axial movements or uniform fracture site compression during dynamization, and the appropriate relaxation of fixator joints to achieve such function, have not been investigated. METHODS: This study used previously developed computational models based on two commercially available unilateral external fixators (Dynafix and Orthofix) to analyze the fixator joint adjustments used and the fracture site movements generated during dynamization. FINDINGS: When none of the fixator's sliding joints were parallel to the long bone axis, significant non-axial movements occurred during dynamization. The dual sliding joint design of the Dynafix fixator was beneficial in reducing these non-axial movements. When all of the fixator joints were allowed to adjust simultaneously during dynamization, exact axial movement or uniform compression at a complicated fracture site was achievable. INTERPRETATION: This study revealed that significant non-axial movements may occur during dynamization, and that such a deficiency can be corrected by relaxing certain fixator joints in addition to the sliding mechanism. The same modeling technique can also be applied in bone lengthening application to assure desirable limb alignment during the distraction process. These analysis results can aid the performance assessment of an external fixator and facilitate appropriate application of such a device to achieve either active or controlled axial movement.

Computer Simulation↗
PubMed2005

Quantification of the microstructural anisotropy of distraction osteogenesis in the rabbit tibia.

A longitudinal orientation of fibers and trabeculae has been observed histologically within distracted callus. This study quantified the intensity and angle of orientation of trabeculae within a distracted callus. Sixteen New Zealand white rabbits underwent unilateral tibial callus distraction with an external fixator across a mid-diaphyseal osteotomy. Included were: a seven-day postoperative latency period, ten days of distraction at 0.5 mm every 12 hours, and 20 days of post-distraction consolidation before euthanasia. Tibiae were removed, stripped of soft tissue, sectioned, and processed for decalcified histology. Micrographs of mid-coronal sections of the callus were evenly divided into 12 regions and underwent Fast Fourier Transform (FFT) analysis of the digitized image to determine the angle and intensity of the orientation of the bony trabeculae within the callus. The microstructure of the regenerate callus demonstrated an angle of orientation that uniformly matched that of cortical bone in all of regions of the callus and an intensity of orientation which approached that of cortical bone.

Animals↗
PubMed2004

The use of Novabone and Norian in cranioplasty: a comparative study.

Bone replacement products have enhanced the ease of reconstructing bone while improving morbidity related to bone harvest. Although these products are successfully used, studies of bone healing and biomechanical strength are lacking. We aimed to compare how Norian CRS (cranial replacement substance) and Novabone C/M heal in a cranial defect. Adult New Zealand rabbits underwent removal of a critical size cranial defect. The defect was filled with Novabone (n = 8), Novabone plus demineralized bone matrix (n = 8), or Norian (n = 8), or it was left empty (n = 8). Rabbits were euthanized at 8 weeks. Cranial specimens were harvested and soft radiographs, contact microradiographs, and biomechanical testing were done. Soft radiographs revealed opacification like adjacent bone with Novabone, which was augmented when Novabone was combined with demineralized bone matrix. Norian maintained an opaque appearance. The control group did not heal. Contact microradiographs demonstrated bone within the healing defect with Novabone, which was augmented by demineralized bone matrix. Norian was not replaced with bone but served as a scaffold for bone formation. Biomechanical indentation testing demonstrated that the stiffness of Norian was the highest. Novabone plus demineralized bone matrix had a higher stiffness than Novabone alone. All experimental groups had a statistically significant difference compared with Norian. None of the groups achieved the strength of unoperated native bone. Studying two popular products, we found evidence that Novabone was incorporated into cranial bone, regenerating the bone. Novabone healed at a faster rate, creating a stronger product, with demineralized bone matrix. The biomechanical strength of the healed defect was higher in the Norian group, because the bone cement remained solid and was not incorporated, unlike crania reconstructed with Novabone.

Animals↗
PubMed2004

Role of guided bone regeneration principle in preventing fibrous healing in distraction osteogenesis at high speed: experimental study in rabbit mandibles.

The formation of fibrous tissues at the distraction gap may result from the accumulation of rapidly migrating fibroblasts at the site of an osteotomy, especially when distraction is rapid. Addition of osteopromotive membranes could theoretically prevent fibroblasts from entering the distraction gap, allowing the osteotomy site to be filled with only osteogenic cells. This study is an attempt to achieve a rapid successful distraction without fibrosis through the use of collagen membranes. Sixteen skeletally mature New Zealand white rabbits were used in this study. They were divided into two groups. One rabbit from each group was excluded from the study because of dislodgement of the distractors. In one group (n = 7), distraction was done as usual. In the other group (n = 7), a collagen membrane surrounded the osteotomy site to be distracted. After a 7-day latency period, distraction started at a rate 2 mm once per day for 5 days. The distractor was left in place for 4 weeks to allow consolidation. Results showed osteogenesis in both groups. Whereas addition of the membrane to distraction increased the quantity of bone formed, absence of the membrane allowed early mineralization (better quality of bone regarding the density). Neither of the two groups showed significant fibrosis or cartilage formation. The endosteum served as a source of blood supply when the periosteum was excluded. The periosteum served as a membrane for guided bone regeneration. Membranes for guided bone regeneration can be used with distraction when the periosteum is lost from trauma or is broken from fast distraction.

Animals↗
PubMed2004

Biomechanical considerations of fracture treatment and bone quality maintenance in elderly patients and patients with osteoporosis.

Osteoporosis is a major public health problem that is characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures of the hip, spine, and wrist. Poor bone quality in patients with osteoporosis presents the surgeon with difficult treatment decisions. Bone fracture repair has more pathways with combinations of bone formation mechanisms, which depend on the type of fracture fixation to be applied to achieve the desirable immobilization. There only may be one remodeling principle and in less than ideal conditions, mechanical and biophysical stimuli may provide effective augmentation of fracture healing in elderly patients. A different stimulus may limit its association to a specific healing mechanism. However, no matter which fixation method is used, an accurate reduction is a requisite for bone healing. Failure to realign the fracture site would result in delayed union, malunion, or nonunion. Therefore, a basic understanding of the biomechanics of osteoporotic bone and its treatment is necessary for clinicians to establish appropriate clinical treatment principles to minimize complications and enhance the patient's quality of life. We describe the biomechanical considerations of osteoporosis and fracture treatment from various aspects. First, bone structure and strength characterization are discussed using a hierarchical approach, followed by an innovative knowledge-based approach for fracture reduction planning and execution, which particularly is beneficial to osteoporotic fracture. Finally, a brief review of the results of several experimental animal models under different fracture types, gap morphologic features, rigidity of fixation devices, subsequent loading conditions, and biophysical stimulation is given to elucidate adverse mechanical conditions associated with different bone immobilization techniques that can compromise normal bone fracture healing significantly.

Aged↗
PubMed2004

Current overview of neurovascular structures in hip arthroplasty: anatomy, preoperative evaluation, approaches, and operative techniques to avoid complications.

Total hip arthroplasty is a common and relatively safe procedure with consistently good results. Despite its popularity and excellent results, THA is a major operation with several major neurovascular structures within reach of retractors, scalpel blades, drills, screws, and reamers. A thorough knowledge of their anatomic location and proximity to the operative field, along with a basic understanding of the principles of vascular surgery can help avoid potentially devastating consequences. Specifically, the surgeon should avoid placement of screws in the anterior-superior quadrant, be vigilant when placing retractors, and avoid excessive tension on the sciatic nerve.

Arthroplasty, Replacement, Hip↗
PubMed2003

Biophysical stimulation of bone fracture repair, regeneration and remodelling.

Biophysical stimulation to enhance bone fracture repair and bone regenerate maturation to restore its structural strength must rely on both the biological and biomechanical principle according to the local tissue environment and the type of mechanical stress to be born by the skeletal joint system. This paper reviews the possible interactions between biophysical stimuli and cellular responses in healing bone fractures and proceeds to speculate the prospects and limitations of different experimental models in evaluating and optimising such non-invasive interventions. It is important to realize that bone fracture repair has several pathways with various combinations of bone formation mechanisms, but there may only be one bone remodeling principle regulated by the hypothesis proposed by Wolff. There are different mechanical and biophysical stimuli that could provide effective augmentation of fracture healing and bone regenerate maturation. The key requirements of establishing these positive interactions are to define the precise cellular response to the stimulation signal in an in vitro environment and to use well-established animal models to quantify and optimise the therapeutic regimen in a time-dependent manner. This can only be achieved through research collaboration among different disciplines using scientific methodologies. In addition, the specific forms of biophysical stimulation and its dose effect and application timing must be carefully determined and validated. Technological advances in achieving focalized stimulus delivery with adjustable signal type and intensity, in the ability to monitor healing callus mechanical property non-invasively, and in the establishment of a robust knowledge base to develop effective and reliable treatment protocols are the essential pre-requisites to make biophysical stimulation acceptable in the main arena of health care. Finally, it is important to bear in mind that successful fracture repair or bone regeneration through callus distraction without adequate remodeling process through physiological loading would seriously undermine the value of biophysical stimulation in meeting the biomechanical demand of a long bone.

Animals↗
PubMed2003

Spring-mediated mandibular distraction osteogenesis.

Successful performance of distraction osteogenesis requires rigorous patient compliance with a daily activation regimen of a percutaneous screw. Previous clinical studies have found that failure of patient compliance with this regimen is the most common complication leading to technical failure of the distraction process. The authors have developed an internalized spring-mediated device for mandibular distraction osteogenesis that can potentially abrogate the risks associated with patient compliance by allowing for automated distraction across an osteotomy. Twenty adult New Zealand White rabbits underwent unilateral mandibular osteotomy. A segment of nickel-titanium shape memory alloy reinforced at both ends with a pinball was fashioned into an inferiorly based arc and secured to the mandible with stainless steel wire. On postoperative day 12, spring activation commenced by cutting a wire binding the two pinballs to one another. Animals were observed for 6 weeks before they were killed. Radiographic studies and decalcified histologic analysis were performed on extracted mandibles. Temperature- and displacement-dependent properties of the shape memory alloy were also examined. Five animals were excluded from the study due to infection, nonunion, or device failure. A mean distraction of 1.2 mm in the distracted hemimandible relative to the nonoperated hemimandible was found (P <.001, two-tailed paired t test). The maximum distraction achieved in an experimental specimen using the spring distractor was 3.7 mm. There were no other histologic or radiographic differences found between study specimens and specimens subjected to traditional distraction methods. Biomechanical testing of the shape memory alloy revealed a temperature-dependent increase in force at body temperature compared with room temperature and a reduction in force with increased displacement of the spring. This study demonstrates the feasibility of spring-mediated distraction osteogenesis across an osteotomy. As the field of distraction osteogenesis matures, the next level of sophistication in the clinical development of devices will incorporate technology that permits fully internalized and automated distraction to occur.

Alloys↗
PubMed2003

Assessment of external fixator reusability using load- and cycle-dependent tests.

No standard method has been established for investigating repeated use of an external fixator. The purpose of the current study was to establish a fatigue testing method for assessing fixator frame reuse. A unilateral DynaFix trade mark external fixator system was tested using high-load and low-cycle (900-150 N at 5 Hz) and low-load and high-cycle (450-100 N at 10 Hz) tests (assumed one use of 500,000 and 1 million cycles, respectively). These loading conditions were selected to simulate single clinical use and to satisfy Food and Drug Administration requirements. In the high-load low-cycle test, substantial failure of the serrated joint occurred before completion of the first simulated use. In the low-load high-cycle test, all fixators completed three simulated clinical uses without failure, although (1/4) of the serrated joint components had hairline cracks. The high-load low-cycle test identified the fixator components which should be examined and replaced if reuse of the fixator is to be considered. Wear and deformation of the set screw on the rotary joint and telescoping mechanisms were observed in the low-load high-cycle test but not in the high-load low-cycle test. Therefore, if the unilateral DynaFix trade mark fixators are being considered for reusability, the number of reuses should be limited as the whole structure of the device will experience fatigue damage as the loading cycle increases.

Analysis of Variance↗
PubMed2003

Effects of selected growth factors on porcine meniscus in chemically defined medium.

Some evidence shows that selected growth factors can increase proteoglycan synthesis and that fibrin clot aids in the repair of meniscal tears. A significant (P<.05) dose-dependent stimulation of proteoglycan synthesis was found with platelet-derived growth factor AB (PDGF-[AB]), transforming growth factor-beta1 and bone morphogenetic protein-7 (osteogenic protein-I). In separate experiments, a significant increase in cellularity was found in the deep and superficial aspects of the explants treated with PDGF-(AB) compared with those treated with basal medium alone. The current study provides data as to which growth factors might prove most useful in the maintenance and repair of menisci.

Animals↗
PubMed2002

Callus stimulation in distraction osteogenesis.

Distraction osteogenesis has been described as in vivo tissue engineering. The ability to stimulate this process for the repair of bony defects or lengthening of congenitally shortened facial structures is likely to significantly impact the field of craniofacial surgery. The purpose of this study was to determine whether mechanical stimulation of the distracted rabbit mandible would accelerate the maturation of the bony callus when applied during the early consolidation period. Twenty adult New Zealand White rabbits underwent unilateral mandibular osteotomy. A uni-directional internal distractor device (Synthes, Paoli, Pa.) was positioned along a plane perpendicular to the line of osteotomy. After a 7-day latency period, distraction was commenced at a rate of 1.0 mm/day for 12 days in all animals. In a control group of 10 rabbits, a consolidation period of 8 weeks was observed before they were killed. In the experimental group of 10 rabbits, daily alternate compression and distraction of 1 mm (sequential compression and distraction) was performed for 3 weeks followed by a 5-week period of rigid fixation. Each animal received a dose of a fluorescent label at three different time points during the study: at the end of the distraction period, 3 weeks after the completion of the distraction phase, and 3 days before it was killed. All animals were killed 8 weeks after the completion of the distraction phase. Undecalcified histologic analysis and 3-point bending tests to failure were performed on the extracted mandibles. The results of the experimental and control groups were compared. Four animals in the control group and three animals in the experimental group were excluded from the study because of screw loosening resulting in distractor dislodgment or because of infection. On histologic analysis, cortical thickness at the center of the callus was found to be significantly greater in the experimental group compared with the control group when normalized to the contralateral hemimandible (83 percent versus 49 percent, respectively; p < 0.007). The ratio of cortical to cancellous bone in the distracted callus was uniformly found to be greater in the experimental specimens. The mineral apposition rate was calculated by using fluorescence microscopy and found to be significantly greater in the experimental group both during the period of sequential compression and distraction (3.2 microm/day versus 2.1 microm/day, p = 0.02) and after the period of sequential compression and distraction (1.4 microm/day versus 1.1 microm/day, p = 0.006). Mechanical testing revealed no significant differences in bending strength or stiffness between experimental or control groups (p = 0.54 and 0.47, respectively). This study has demonstrated that daily alternating compression and distraction of 1 mm amplitude during the early consolidation period has a stimulatory impact on callus formation with respect to osteoblastic activity, remodeling, and maturation of bone. Optimal timing and amplitude of sequential movement, long-term biomechanical differences, and molecular pathways have yet to be elucidated.

Animals↗
PubMed2002

Recovery from osteoporosis through skeletal growth: early bone mass acquisition has little effect on adult bone density.

It is often assumed that bone mineral accretion should be optimized throughout childhood to maximize peak bone mass. In contrast, we hypothesized that bone mineral acquisition early in life would have little or no effect on adult bone mass because many areas of the juvenile skeleton are replaced in toto through skeletal growth. To test this hypothesis, we induced osteoporosis by administering dexamethasone to 5-week-old rabbits for 5 weeks and then allowed them to recover for 16 weeks. Tibial bone mineral density (ash weight/volume) was decreased in the dexamethasone-treated animals at the end of treatment but recovered completely. Bone structure in the femur was assessed by histomorphometry. Trabecular and cortical bone in the distal metaphysis was made osteoporotic by dexamethasone, but was then replaced through endochondral bone formation and recovered. Periosteal bone formation rate in the diaphysis was decreased during dexamethasone treatment but afterwards rebounded above controls and normalized cortical width. Our data suggest that bone mineral acquisition early in life has little effect on adult bone density because the juvenile bone is largely replaced through growth. If this concept generalizes, then interventions to maximize peak bone mass should be directed at adolescents rather than young children.

Animals↗