Intact Femur Research Articles

Improved mechanical long-term reliability of hip resurfacing prostheses by using silicon nitride

Although ceramic prostheses have been successfully used in conventional total hip arthroplasty (THA) for many decades, ceramic materials have not yet been applied for hip resurfacing (HR) surgeries. The objective of this study is to investigate the mechanical reliability of silicon nitride as a new ceramic material in HR prostheses. A finite element analysis (FEA) was performed to study the effects of two different designs of prostheses on the stress distribution in the femur-neck area. A metallic (cobalt-chromium-alloy) Birmingham hip resurfacing (BHR) prosthesis and our newly designed ceramic (silicon nitride) HR prosthesis were hereby compared. The stresses induced by physiologically loading the femur bone with an implant were calculated and compared with the corresponding stresses for the healthy, intact femur bone. Here, we found stress distributions in the femur bone with the implanted silicon nitride HR prosthesis which were similar to those of healthy, intact femur bone. The lifetime predictions showed that silicon nitride is indeed mechanically reliable and, thus, is ideal for HR prostheses. Moreover, we conclude that the FEA and corresponded post-processing can help us to evaluate a new ceramic material and a specific new implant design with respect to the mechanical reliability before clinical application.

Effects of Prosthesis Stem Materials on Stress Distribution of Total Hip Replacement

Bone loss and bone thickening phenomenon occurred due to different stiffness of the implant and femur. Implant with stiffer materials than the bone carries majority of the load and it transferred down along the implant till the distal tip of the stem. Both phenomenons contribute to stress shielding and loosening of the prosthesis stem. In this study, the stress distributions in intact femur and THR femur are established using finite element method. The THR femur model consists of cemented hip Ti6Al4V and CoCrMo prosthesis stem implanted inside the femur bone. Effects of different material properties of the prosthesis stem on the resulting stress distributions are investigated. Results shows that the largest discrepancy in stress values between intact and THR femur is predicted along the middle region at both lateral and medial planes. The distal region shows that the calculated stress for both THR femur experienced higher stress magnitude than that of intact femur. The higher stress in THR femur leads to bone thickening at the particular region. The corresponding stress magnitude saturates at 25 MPa for THR femur while intact femur is slightly lower at 22 MPa.

Biomechanical strain analysis of the proximal femur after retrograde intramedullary nailing

BACKGROUND: The purpose of this study was to examine the influence of proximal retrograde intramedullary nail position on proximal femoral strain, since stress risers occurring at the end of an implant can increase fracture risk. METHODS: Proximal femoral strains during axial and torsional loading were measured in composite Sawbone femurs after placement of retrograde intramedullary nails that ended at three different locations (2 cm proximal, 4 cm distal, and at the level of the lesser trochanter). RESULTS: No statistically significant difference was found between the axial or torsional strain observed in the intact femur and that seen after placement of a retrograde femoral nail ending at any of the three positions. Gages proximal to the nail tip demonstrated higher strains than the strains for the intact femur when compared with gages distal to the nail tip. CONCLUSION: The ending location of a retrograde nail in the proximal femur does not appear to significantly alter strain in the proximal femur under the axial and torsional loading methods used in the study.

Temporal and spatial expression of osteoactivin during fracture repair

We previously identified osteoactivin (OA) as a novel secreted osteogenic factor with high expression in developing long bones and calvaria, and that stimulates osteoblast differentiation and matrix mineralization in vitro. In this study, we report on OA mRNA and protein expression in intact long bone and growth plate, and in fracture calluses collected at several time points up to 21 days post-fracture (PF). OA mRNA and protein were highly expressed in osteoblasts localized in the metaphysis of intact tibia, and in hypertrophic chondrocytes localized in growth plate, findings assessed by in situ hybridization and immunohistochemistry, respectively. Using a rat fracture model, Northern blot analysis showed that expression of OA mRNA was significantly higher in day-3 and day-10 PF calluses than in intact rat femurs. Using in situ hybridization, we examined OA mRNA expression during fracture healing and found that OA was temporally regulated, with positive signals seen as early as day-3 PF, reaching a maximal intensity at day-10 PF, and finally declining at day-21 PF. At day-5 PF, which correlates with chondrogenesis, OA mRNA levels were significantly higher in the soft callus than in intact femurs. Similarly, we detected high OA protein immunoexpression throughout the reparative phase of the hard callus compared to intact femurs. Interestingly, the secreted OA protein was also detected within the newly made cartilage matrix and osteoid tissue. Taken together, these results suggest the possibility that OA plays an important role in bone formation and serves as a positive regulator of fracture healing.

Role of the N- and C-terminal Fragments of Parathyroid-Hormone-Related Protein as Putative Therapies to Improve Bone Regeneration Under High Glucocorticoid Treatment

The parathyroid-hormone-related protein (PTHrP) is an important modulator of bone formation and bone remodeling. High and/or prolonged glucocorticoid (GC) treatments inhibit PTHrP expression in osteoblastic cells and bone formation and repair. We assessed the ability of the N- and C-terminal PTHrP fragments to restore the GC-altered bone regeneration after bone marrow ablation in mice. Animals were administered 3-methylprednisolone or vehicle and PTHrP (1-36) or PTHrP (107-139) every other day, beginning 4 days before marrow ablation in the tibia, and euthanized 12 days later. GC-treated mice showed in the ablated tibia a decrease in bone formation and in osteoblast and sclerostin-positive osteocyte numbers, reduced expression of osteoblastic factors, decreased osteogenesis of bone-marrow-derived cells, an increase in the numbers of multinucleated osteoclasts and adipocytes, and decreased cortical vascularization, as well as altered bone structure (measured by microcomputerized tomography) in the intact femur. These effects were reversed at least in part by either PTHrP peptide. The present novel findings support the use of both PTHrP peptides tested as putative bone regenerative therapies in GC-related bone diseases.

Design considerations for ceramic resurfaced femoral head: effect of interface characteristics on failure mechanisms

Ceramic hip resurfacing may offer improved wear resistance compared to metallic components. The study is aimed at investigating the effects of stiffer ceramic components on the stress/strain-related failure mechanisms in the resurfaced femur, using three-dimensional finite element models of intact and resurfaced femurs with varying stem–bone interface conditions. Tensile stresses in the cement varied between 1 and 5 MPa. Postoperatively, 20–85% strain shielding was observed inside the resurfaced head. The variability in stem–bone interface condition strongly influenced the stresses and strains generated within the resurfaced femoral head. For full stem–bone contact, high tensile (151–158 MPa) stresses were generated at the cup–stem junction, indicating risk of fracture. Moreover, there was risk of femoral neck fracture due to elevated bone strains (0.60–0.80% strain) in the proximal femoral neck region. Stresses in the ceramic component are reduced if a frictionless gap condition exists at the stem–bone interface. High stresses, coupled with increased strain shielding in the ceramic resurfaced femur, appear to be major concerns regarding its use as an alternative material.

Femoral Cortical Stress Lesions in Long-Term Bisphosphonate Therapy: A Herald of Impending Fracture?

Lateral cortical stress reactions have been documented to precede femoral insufficiency fractures after long-term bisphosphonate therapy. We studied the natural history of femoral stress lesions associated with long-term bisphosphonate therapy. A retrospective clinical and radiologic review of all patients with radiologically documented femoral stress lesions associated with bisphosphonate therapy was carried out in a tertiary center involved with geriatric trauma care. Of 1463 geriatric hip fractures occurring from May 1, 2004, to July 31, 2008, 33 were of a distinct metaphyseal-diaphyseal configuration. Thirty-two were on prior bisphosphonate therapy. Sixteen femurs showed a lateral cortical thickening either on prefracture radiographs (four femurs) or on radiographs of the contralateral femur (12 femurs). Features that predispose to complete stress fractures were determined. The intact femurs were followed up for symptomatic and radiologic progression and occurrence of new lesions. All four cases that fractured had a "dreaded black line" in the lesion, whereas only 1 of 12 patients had this fracture in femurs which remained intact (100% versus 8.3%, P = 0.003). All patients who fractured reported thigh discomfort over 1 month (range, 0.1-9.0 months; standard deviation, 4.0 months), whereas three of 12 patients who did not fracture reported thigh discomfort (100% versus 25%, P = 0.019). In the remaining patients, eight patients were asymptomatic, two patients had reduced symptoms, and one patient had persistent thigh pain at 23.0 months (range, 5-35 months; standard deviation, 10.2 months). One patient was too demented for symptomatic assessment. No patient developed a new lesion. Radiologic stabilization of the lateral cortical thickening was evident on follow-up radiographs. Cortical stress reactions associated with prolonged antiresorptive therapy, in the presence of pain and the "dreaded black line," have an increased risk for complete stress fractures.

Medial Femoral Condyle Strength After Tunnel Placement for Single- and Double-Bundle Posterior Cruciate Ligament Reconstruction

Single-bundle posterior cruciate ligament (PCL) reconstruction can restore normal posterior laxity; double-bundle reconstruction is needed to more closely mimic normal knee kinematics. Drilling two tunnels removes additional bone from the medial femoral condyle and may interfere with its vascular supply, increasing the risk of fracture or subchondral collapse. Three groups of seven synthetic femurs were tested: no tunnels, single anterolateral 10-mm tunnel, and double tunnel (anterolateral 10-mm tunnel and posteromedial 8-mm tunnel). The distal femur was potted to rigidly hold each specimen during testing. Compressive loading was performed at 2 mm/minute using an Instron (Instron Corp, Canton, Mass). Load and displacement at failure were recorded; stiffness was calculated from those measurements. Mean failure load of the double-tunnel group (7705 N) was significantly lower than the intact group (10962 N, P < .008). No other significant differences were detected. In this model, the double-bundle technique significantly reduced failure force, increasing the potential risk of medial femoral condyle fracture compared to the intact femur. The double-bundle technique also trended toward reduced stiffness. Therefore, a period of postoperative protected weight bearing is recommended.

Conditional Disruption of Pkd1 in Osteoblasts Results in Osteopenia Due to Direct Impairment of Bone Formation

PKD1 (polycystin-1), the disease-causing gene for ADPKD, is widely expressed in various cell types, including osteoblasts, where its function is unknown. Although global inactivation of Pkd1 in mice results in abnormal skeletal development, the presence of polycystic kidneys and perinatal lethality confound ascertaining the direct osteoblastic functions of PKD1 in adult bone. To determine the role of PKD1 in osteoblasts, we conditionally inactivated Pkd1 in postnatal mature osteoblasts by crossing Oc (osteocalcin)-Cre mice with floxed Pkd1 (Pkd1(flox/m1Bei)) mice to generate conditional heterozygous (Oc-Cre;Pkd1(flox/+)) and homozygous (Oc-Cre;Pkd1(flox/m1Bei)) Pkd1-deficient mice. Cre-mediated recombination (Pkd1(Delta flox)) occurred exclusively in bone. Compared with control mice, the conditional deletion of Pkd1 from osteoblasts resulted in a gene dose-dependent reduction in bone mineral density, trabecular bone volume, and cortical thickness. In addition, mineral apposition rates and osteoblast-related gene expression, including Runx2-II (Runt-related transcription factor 2), osteocalcin, osteopontin, and bone sialoprotein, were reduced proportionate to the reduction of Pkd1 gene dose in bone of Oc-Cre;Pkd1(flox/+) and Oc-Cre;Pkd1(flox/m1Bei) mice. Primary osteoblasts derived from Oc-Cre;Pkd1(flox/m1Bei) displayed impaired differentiation and suppressed activity of the phosphatidylinositol 3-kinase-Akt-GSK3beta-beta-catenin signaling pathways. The conditional deletion of Pkd1 also resulted in increased adipogenesis in bone marrow and in osteoblast cultures. Thus, PKD1 directly functions in osteoblasts to regulate bone formation.

The effect of cortex thickness on intact femur biomechanics: A comparison of finite element analysis with synthetic femurs

Biomechanical studies on femur fracture fixation with orthopaedic implants are numerous in the literature. However, few studies have compared the mechanical stability of these repair constructs in osteoporotic versus normal bone. The present aim was to examine how changes in cortical wall thickness of intact femurs affect biomechanical characteristics. A three-dimensional, linear, isotropic finite element (FE) model of an intact femur was developed in order to predict the effect of bicortical wall thickness, t, relative to the femur's mid-diaphyseal outer diameter, D, over a cortex thickness ratio range of 0 < or = t/D < or = 1. The FE model was subjected to loads to obtain axial, lateral, and torsional stiffness. Ten commercially available synthetic femurs were then used to mimic 'osteoporotic' bone with t/D = 0.33, while ten synthetic left femurs were used to simulate 'normal' bone with t/D = 0.66. Axial, lateral, and torsional stiffness were measured for all femurs. There was excellent agreement between FE analysis and experimental stiffness data for all loading modes with an aggregate average percentage difference of 8 per cent. The FE results for mechanical stiffness versus cortical thickness ratio (0 < or = t/D < or = 1) demonstrated exponential trends with the following stiffness ranges: axial stiffness (0 to 2343 N/mm), lateral stiffness (0 to 62 N/mm), and torsional stiffness (0 to 198 N/mm). This is the first study to characterize mechanical stiffness over a wide range of cortical thickness values. These results may have some clinical implications with respect to appropriately differentiating between older and younger human long bones from a mechanical standpoint.

Healing of Large Segmental Bone Defects Induced by Expedited Bone Morphogenetic Protein-2 Gene-Activated, Syngeneic Muscle Grafts

Numerous preclinical studies have shown that osseous defects can be repaired by implanting bone morphogenetic protein (BMP)-2-transduced muscle cells. However, the drawback of this treatment modality is that it requires the isolation and long-term (approximately 3 weeks) culture of transduced autologous cells, which makes this approach cumbersome, time-consuming, and expensive. Therefore, we transferred BMP-2 cDNA directly to muscle tissue fragments that were held in culture for only 24 hr before implantation. We evaluated the ability of such gene-activated muscle grafts to induce bone repair. Two of 35 male, syngeneic Fischer 344 rats used in this study served as donors for muscle tissue. The muscle fragments remained unmodified or were incubated with an adenoviral vector carrying the cDNA encoding either green fluorescent protein (GFP) or BMP-2. Critical-size defects were created in the right femora of 33 rats and remained untreated or were filled (press fitted) with either unmodified muscle tissue or GFP-transduced muscle tissue or with BMP-2-activated muscle tissue. After 6 weeks, femora were evaluated by radiography, microcomputed tomography (muCT), histology, and biomechanical testing. Six weeks after implantation of BMP-2-activated muscle grafts, 100% of the bone defects were bridged, as documented by radiographs and muCT imaging, and showed formation of a neocortex, as evaluated by histology. Bone volumes of the femora repaired by BMP-2-transduced muscle were significantly (p = 0.006) higher compared with those of intact femora and the biomechanical stability was statistically indistinguishable. In contrast, control defects receiving no treatment, unmodified muscle, or GFP-transduced muscle did not heal. BMP-2 gene-activated muscle grafts are osteoregenerative composites that provide an expedited means of treating and subsequently healing large segmental bone defects.

Ability of Recombinant Human Bone Morphogenetic Protein 2 to Enhance Bone Healing in the Presence of Tobramycin: Evaluation in a Rat Segmental Defect Model

To determine whether locally applied tobramycin influences the ability of recombinant human bone morphogenetic protein 2 (rhBMP-2) to heal a segmental defect in the rat femur. The influence of tobramycin on the osteogenic differentiation of mesenchymal stem cells was first evaluated in vitro. For the subsequent, in vivo experiments, a 5-mm segmental defect was created in the right femur of each of 25 Sprague-Dawley rats and stabilized with an external fixator and four Kirschner wires. Rats were divided in four groups: empty control, tobramycin (11 mg)/absorbable collagen sponge, rhBMP-2 (11 microg)/absorbable collagen sponge, and rhBMP-2/absorbable collagen sponge with tobramycin. Bone healing was monitored by radiography at 3 and 8 weeks. Animals were euthanized at 8 weeks and the properties of the defect were compared with the intact contralateral femur. Bone formation in the defect region was assessed by dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing. Tobramycin exerted a dose-dependent inhibition of alkaline phosphatase induction and calcium deposition by mesenchymal stem cells cultured under osteogenic conditions. The inhibition was reversed in the presence of 500 ng/mL of rhBMP-2. Segmental defects in the rat femora failed to heal in the absence of rhBMP-2. Tobramycin exerted no inhibitory effects on the ability of rhBMP-2 to heal these defects and increased the bone area of the defects treated with rhBMP-2. Data obtained from all other parameters of healing, including dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing, were unaffected by tobramycin. Although our in vitro results suggested that tobramycin inhibits the osteogenic differentiation of mesenchymal stem cells, this could be overcome by rhBMP-2. Tobramycin did not impair the ability of rhBMP-2 to heal critical-sized femoral defects in rats. Indeed, bone area was increased by nearly 20% in the rhBMP-2 group treated with tobramycin. This study shows that locally applied tobramycin can be used in conjunction with rhBMP-2 to enhance bone formation at fracture sites.

A finite element analysis of stress distribution on proximal femur after vulgus implantation in hip resurfacing arthroplasty

Objective To determine an ideal angle for prosthesis implantation after analyzing the stress distribution on the proximal femur after valgus implantation of hip resurfacing arthroplasty.Methods A three-dimensional finite element model of intact femur was developed for implantation of the Wright hip resudaeing prosthesis at valgus degrees of 0°,5°,10°,and 15°.After articular resultant forces and related muscles' forces were loaded,changes in stresses on the proximal femur before and after implantation were analyzed.Results A slightly valgus orientation reduced the stress on the superior neck around the head-neck junction (sections 2 & 8).In the implantation at valgus degrees of 5°,the stress shielding in the proximal sections (sections 1 & 7) was the minimum,and the stress distribution in sections 4 and 10 were close to that in the case of an intact femur.Conclusion A valgus 5° implantation in hip resudacing arthroplasty may result in a stress distribution on the proximal femur similar to the normal value and thus may decrease the risks of femoral neck fracture and aseptic loosening of the femoral component. Key words: Arthroplasty,replacement,hip; Prosthesis implantation; Femur; Finite element analysis

The Early Effects of Intramedullary Reaming of the Femur on Bone Mineral Density; an Experimental Study in Pigs

Both fracture and fracture treatment affect bone mineral density (BMD). BMD after standard intramedullary reaming of the femoral cavity and after reaming with a reamer-irrigator-aspirator (RIA) system were studied with the hypothesis that the RIA technique would lead to lower BMD levels. Dual-energy X-ray absorptiometry (DXA) was performed on the third day after operation with standard intramedullary nailing technique (n = 6) or RIA technique (n = 7) in intact femora of young Norwegian landrace pigs. Significantly lower BMD were found in the mid-shaft and total femur after reaming with the RIA technique compared to the non-operated femur. Traditional reaming technique resulted in significantly higher BMD in the distal -femur. The results of this study indicate that standard reaming increased BMD in the distal femur, suggesting compressive effects on trabecular bone. The RIA technique decreased BMD in the femoral diaphysis and total femur, suggesting removal of trabecular bone. A possible clinical impact of the findings remains to be investigated.

PET Imaging of Leptin Biodistribution and Metabolism in Rodents and Primates

We have determined the systemic biodistribution of the hormone leptin by PET imaging. PET imaging using (18)F- and (68)Ga-labeled leptin revealed that, in mouse, the hormone was rapidly taken up by megalin (gp330/LRP2), a multiligand endocytic receptor localized in renal tubules. In addition, in rhesus monkeys, 15% of labeled leptin localized to red bone marrow, which was consistent with hormone uptake in rodent tissues. These data confirm a megalin-dependent mechanism for renal uptake in vivo. The significant binding to immune cells and blood cell precursors in bone marrow is also consistent with prior evidence showing that leptin modulates immune function. These experiments set the stage for similar studies in humans to assess the extent to which alterations of leptin's biodistribution might contribute to obesity; they also provide a general chemical strategy for (18)F labeling of proteins for PET imaging of other polypeptide hormones.

Effects of neuropeptides and vasoactive substances on microcirculation of the callus after tibial osteotomy in rabbits

Previous studies have demonstrated a dynamic ingrowth of vessels into the developing callus. In this study, maturation and development of the regulation of microcirculation were followed in the callus of rabbits. In the first series, the effects of vasoactive substances on blood flow velocity, perfusion pressure, duration of effects and peripheral vascular resistance of the bone marrow in the femur and tibia were compared. In the second series, the same parameters were measured in the femur and in the developing callus 10 and 15 days following gap osteotomy of the tibia. There were no significant differences between the microcirculatory reactions of the intact femur and tibia. Basal blood flow could be verified in the callus on the 10th postoperative day. No vascular reactions could be elicited. Basal blood flow velocity was higher on the 15th day, when compared to the measurements on the 10th day. The substances elicited statistically significant differences in flow velocity, resistance and 50% recovery time in the callus on the 15th day. Blood flow reactions of the ipsilateral femoral and tibial bone marrow are identical, thus the femur can serve as a reference site for blood flow measurements in the callus. Regulation and maturation of callus microcirculation develop rapidly between the 10th and 15th days.

An in vitro study of the strain distribution in human femora with anatomical and customised femoral stems

Hydroxyapatite-coated standard anatomical and customised femoral stems are designed to transmit load to the metaphyseal part of the proximal femur in order to avoid stress shielding and to reduce resorption of bone. In a randomised in vitro study, we compared the changes in the pattern of cortical strain after the insertion of hydroxyapatite-coated standard anatomical and customised stems in 12 pairs of human cadaver femora. A hip simulator reproduced the physiological loads on the proximal femur in single-leg stance and stair-climbing. The cortical strains were measured before and after the insertion of the stems. Significantly higher strain shielding was seen in Gruen zones 7, 6, 5, 3 and 2 after the insertion of the anatomical stem compared with the customised stem. For the anatomical stem, the hoop strains on the femur also indicated that the load was transferred to the cortical bone at the lower metaphyseal or upper diaphyseal part of the proximal femur. The customised stem induced a strain pattern more similar to that of the intact femur than the standard, anatomical stem.

Shock waves micro‐damage induction in cortical bones: Comparison between experimental and simulations results.

Shock waves (SW) are considered a promising method to treat bone non unions. One potential mechanisms of action is the initiation of local micro‐fractures, which may in turn trigger the start of bone healing. In this study, a set of eight intact rat femurs have been subjected to SWs (peak positive pressure of 40 MPa and peak negative pressure of −8 MPa, PRF of 2 Hz). The number of SW was varied from 50 to 1500. Micro‐CT images of the specimens were acquired before and after treatment (16 microns resolution). In parallel, numerical simulations were used to quantify the stresses induced by SWs in cortical bone tissue. We used a 3‐D FDTD code to solve the linear lossless equations that describe wave propagation in solids and fluids. A 3‐D model of a fractured rat femur was obtained from micro‐CT data. Results demonstrate that damages were induced in the bone tissues from 150 SWs. Comparison of the location of the induced damages on micro‐CT images with predictions of maximum stresses by numerical simulations...

Effects of Positioning and Notching of Resurfaced Femurs on Femoral Neck Strength: A Biomechanical Test

To assess the effects of positioning and notching of resurfaced femurs on the mechanical strength of third-generation saw bone (TGSB) femurs using an in vitro analogue bone model. 30 TGSB femurs were equally divided into 6 resurfaced femur groups (intact, anatomic, varus, valgus, anatomically notched, and valgus notched) for testing the load to failure, stiffness, and total energy. Compared to the intact femurs, the load to failure in all resurfaced femurs was significantly decreased by 29 to 57%. Among the resurfaced femurs, valgus and anatomic femurs had the highest load to failure, followed by valgus notched, varus, and anatomically notched femurs. Notching weakened the construct by a further 24 to 30%. To minimise the risk of femoral neck fracture, resurfaced femoral heads should be placed in an anatomic or valgus orientation, and the superior cortex of the femoral neck should remain intact.

OP-1 Augments Glucocorticoid-inhibited Fracture Healing in a Rat Fracture Model

Glucocorticoids inhibit bone remodeling and fracture healing. We sought to determine whether osteogenic protein 1 (OP-1) can overcome this inhibition in a closed fracture model in the rat. Time-released prednisolone or placebo pellets were implanted subcutaneously; closed femoral fractures were created 2 weeks later in rats. Fractures received sham, OP-1 and collagen, or collagen-only implants. Femurs were harvested at 3, 10, 21, 28, and 42 days postfracture. Fractures were examined radiographically for amount of hard callus; mechanically for torque and stiffness (also expressed as a percentage of the contralateral intact femur); and histomorphometrically for amount of cartilaginous and noncartilaginous soft callus, hard callus, and total callus. Glucocorticoid administration inhibited fracture healing. The application of a devitalized Type I collagen matrix mitigated the inhibitory effects of prednisolone on fracture healing However, further increases in indices of fracture healing were observed when OP-1 was added to the collagen matrix compared with collagen alone. OP-1 and collagen was more effective than collagen alone.