Introduction. Failures in fracture healing are mainly caused by a lack of neovascularization. We have previously demonstrated that G-CSF-mobilized peripheral blood (GM-PB) CD34+ cells, an endothelial progenitor enriched cell population, contributed to fracture healing via vasculogenesis and osteogenesis. We postulated the hypothesis that local transplantation of culture expanded bone marrow (cEx-BM) CD34+ cells could exhibit therapeutic potential for fracture healing. Materials. BM CD34+ cells were cultured in specific medium with 5 growth factors for 1week. A reproducible model of femoral fracture was created in nude rats with periosteum cauterization, which leads to nonunion at 8 weeks post-fracture. Rats received local administration of the following cells or PBS alone(1)cEx-BM, (2)BM, (3)GM-PB CD34+ cells or (4)PBS. Results. Our 7-day culture expansion technique allowed us to obtain 23 times of BM CD34+ cells maintaining 60% purity of CD34 positivity. cEx-BM CD34+ cells exhibited striking therapeutic efficacy for unhealing fracture promoting neovascularization and osteogenesis in sites of fracture. Moreover, cEx-BM CD34+ cells showed high capacity of colony formation and osteogenic differentiation. Conclusion. BM CD34+ cells can be obtained from the fracture site at the time of primary operation and stored for further use, autologous culture expanded BM CD34+ cell transplantation therapy would be not only a simple but also powerful therapeutic strategy for unhealing fracture

Introduction. Nonunions pose complications in fracture management that can be treated using electrical stimulation (ES). Bone marrow mesenchymal stem cells (BMMSCs) are essential in fracture healing, although the effects of different clinical ES waveforms available in clinical practice on BMMSCs cellular activities is unknown. Materials and Methods. We compared Direct Current (DC), Capacitive Coupling (CC), Pulsed Electromagnetic wave (PEMF) and Degenerate Wave (DW) by stimulating human-BMMSCs for 5 days for 3 hours a day. Cytotoxicity, cell proliferation, cell-kinetics and cell apoptosis were evaluated after ES. Migration and invasion were assessed using fluorescence microscopy and affected gene and protein expression were quantified. Results. DW had the greatest proliferative and least apoptotic and cytotoxic effects compared to other waveforms and unstimulated cells after 5 days of ES (p < 0.001). DC, DW and CC resulted in significantly more cells in S phase and G2/M phase (p < 0.01) compared to the unstimulated BMMSCs. CC and DW caused more cells to invade collagen and showed increased MMP-2 and MT1-MMP expression (p < 0.001) compared to the other waveforms and unstimulated BMMSCs. DC increased cellular migration in a scratch-wound assay and all ES waveforms increased migration gene expression with DC having the greatest effect (p < 0.01). Conclusion. The ES waveform is vital in influencing BMMSCs cellular activities. Migration and invasion were increased by ES which suggests that the recruitment of BMMSCs to the healing site during a fracture could be increased by ES

Introduction. The concept of “bone graft expanders” has been popularised to increase the volume and biological activity of the implanted Material. HYPOTHESIS. Orthoss® granules support exogenously seeded MSCs and attract neighbouring host MSCs. Methods. In 3-D cultures’ Orthoss® granules were seeded with 2×10. 5. bone marrow MSCs/granule and maintained in MSC expansion or differentiation media for 21 days. In homing experiments’ bone autografts were placed in close proximity to Orthoss®. Scaffold colonisation and MSC differentiation were assessed by confocal microscopy’ standard electron microscopy’ and energy-dispersive X-ray spectroscopy. Results. Long-term incubation of MSC/scaffold resulted in formation of multiple cell-matrix layers lining the scaffold pores as well as outer surfaces. MSC differentiation to osteoblasts was evident as strong deposition of Calcium and Phosphorus was detected in both MSC expansion and osteogenic conditions. Cell egress experiments demonstrated the migration of cells from neighbouring autografts and their attachment and re-settlement on Orthoss®. Discussion & Conclusions. Orthoss® scaffolds support MSC attachment’ growth and osteogenic differentiation whereas resident bone subpopulations can rapidly migrate towards’ attach’ and expand on them. These results indicate that Orthoss® can serve as a graft expander for repairing large bone defects in trauma patients

Introduction. The delay looks radiographically as a fracture callus not very evident or absent 6 months after osteosynthesis. Patients undergo a long period of immobilization and this fact causes the increase the social cost of the disease. The technique we suggest aims to the reduce the period of immobilization and as a consequence the management costs of the disease. Materials and methods. Our technique includes the infiltration of the delay focus with platelet rich fibrin, bone marrow concentrated and demineralized bone matrix. Outpatients and radiographic checks were carried out 3, 6 and 12 months after surgery. The treatment was considered fail in case of absence of bone callus at 3 out of 4 corticals at the rx after 6 months from surgery. Results. From November 2008 we treated 14 patients (average age 35 years, range 18 to 53). The treatment was performed after an average period of 14 months (range 5 to 38) from the fracture. The average follow up was 12 months (range 3–30). After 3 months from surgery, seven patients bear full load, did not feel pain and X-ray showed an increase of osteogenesis. Two cases failed; in one of them the patient underwent another infiltration and in the other one we replaced the fixation. Conclusion. Our tecnique lets a reduction of healing times in patients with delay and can be performed through the One Day Surgery programme

Introduction. This study reports the results of percutaneous autologous bone marrow grafting in 62 patients with corticosteroids treatment who had one hip osteonecrosis treated with bone marrow (BM) injection and the other contralateral hip osteonecrosis with core decompression (CD) alone. Only patients with bilateral symptomatic osteonecrosis and with those hips at stage I or II (as defined by Steinberg) were included in this study. Material and Methods. Between 1988 and 1995, 62 consecutive patients (28 males and 34 females) were included in this study. These patients had a mean age of 31 years (range 18 to 34 years) at the time of the onset of symptoms. The average follow-up was 17 years (range, 15 to 20 years). An average of 152 + 16 milliliters of marrow was aspirated from the iliac crest. The number of stroma progenitor that was transplanted was estimated by counting the Fibroblast Colony Forming Units which express type I and type III collagen. The bone marrow graft obtained after concentration contained average 4889 + 716 progenitors per cubic centimeter (range 3515 to 6293 per cubic centimeter). Each hip received a mean number of thirty cubic centimeters of bone marrow graft (range 27 to 35 cubic centimeters). The average total number of CFU-F injected in each hip was therefore 147 × 103 cells (range 119 × 103 to 195 × 103 cells). Results. Clinical results were determined by the change in Harris hip scores from preoperative evaluation to the last follow-up visit, by the change in the radiographic progression and by the need of subsequent total hip arthroplasty. Bone marrow grafting afforded better reduction in pain, effected a reduction with time in the number of hips that progressed to collapse, and delayed the need for total hip replacement. Ten hips had collapsed and needed arthroplasty at the most recent follow-up after bone marrow grafting, compared to 45 after core decompression. For hips with collapse, the mean survival time before collapse was 71.2 months (43.35- 60.96; 95% CI) for the bone marrow graft group and 38.5 months for the control group (13.2–39.74; 95% CI). With the number available, there was a positive correlation (Spearman's test) between the duration of clinical survival before collapse and the number or concentration of CFU-F and CFU-GM in the graft in the CD group. These results are explained by the fact that bone marrow injection improved the repair process on MRI and on histology. Overall, 10 hips with bone marrow injection showed a total regression of the signal, 59 hips showed a partial reduction (42 with BM and 17 with CD) and 55 hips did not show a significant reduction (10 with BM and 45 with CD). Conclusion. Bone marrow grafting afforded better reduction in pain, reduction in the number of collapses, delayed the need for total hip replacement, and improved the repair process on MRI and on histology

Periprosthetic osteolysis depends on the biological activity of wear particles, but there is little known about the distribution of polyethylene wear particles (PE) in the surrounding joint tissue. The purpose of this study was to examine the localisation of wear particles of six different PEs, including four crosslinked polyethylenes (XPE), as well as their biological activity in the murine knee. Material and Methods. Wear particles of 4 XPE- and 2 UHMWPE-inserts were isolated (knee joint simulator). For all groups the particles were similar in size and shape (mean diameter 0.3–05μm; 20nm-nucleopore-filter; ISO; n = 100.000).56 female Balb/c mice were randomly assigned to six treatment groups and one control group: control (PBS), XPE1 (3×30 kGy Gamma, annealed/sequential irradiated), XPE2 (95 kGy E-beam, remelted), XPE3 (65 kGy E-beam, remelted), XPE 4 (50 kGy Gamma, remelted), UHMWPE 1, UHMWPE 2. 50 μl of each particle suspension [(0.1% vol/vol (particle volume/PBS volume) after removal of endotoxin] were injected into the left knee joint. After 1 week the mice were killed and a histological and immunhistochemical analysis of the knee joints was done (IL-1, TNF-, ICAM-1). For the immunhistochemistry the articular cartilage, the bone marrow and the synovial membrane were evaluated semiquantitatively (Kruskal-Wallis test; all pairwise multiple comparison procedure; Bonferoni correction; significance level: p<0.05). Results. All groups showed a thickened synovial layer with an increased cellular infiltration. The particles of XPE 1 and 2 were localised in the bone marrow as well as in the joint space. In contrast, the particles of XPE 3 and 4 were distributed in the synovial layer and in the bone marrow as well, but not in the joint space. The UHMWPE1 particles were mainly located in the bone marrow and joint space while the UHMWPE2 particles were mainly found in the bone marrow and the synovial layer. For all PE groups there was a higher cytokine expression compaired to control (p<0.0024) without any differences between the groups (bone marrow/synovial layer). The chondrocytes in the groups with XPE 1- and XPE 2-particles expressed more TNF- than in the control group and the other treatment groups (p = 0.000). Conclusion. XPEs lead to a similar inflammatory reaction in vivo compared to conventional polyethylenes. The high TNF- expression in the articular cartilage (groups XPE 1 and 2) might be explained by the localisation of the wear particles in the joint space in direct contact with the chondrocytes. Long-term studies are necessary to analyse the effects of different wear particle distributions in the joint surrounding tissue after knee and hip replacement. Furthermore it has to be investigated, whether their distribution in the joint space or their transport into the bone marrow is responsible for the level of the chronic inflammatory reaction

The burden of osteoporosis (OP), and its accompanied low energy fractures, is ever increasing. Targeted therapies are under development to stem the tide of the disease, with microRNAs identified as biomarkers and potential targets. Assessing the functional capacity of bone marrow mesenchymal stromal cells (BMSC) from patients with low energy neck of femur fractures (NOF) will identify the expected outcomes to be achieved from new, targeted osteogenic therapies. Two patient groups were assessed; low energy NOF and osteoarthritic. Bone marrow aspirates were taken at time of arthroplasty surgery. The adherent fraction was cultured and assessed by flow cytometry, microRNA expression and differentiation functionality. Both patient groups demonstrated characteristic extracellular markers of BMSCs. 3 key markers were significantly reduced in their expression in the NOF group (CD 90, 13, 166 P=0.0286). Reduced differentiation capacity was observed in the NOF group when cultured in osteogenic and adipogenic culture medium. 105 microRNAs were seen to be significantly dysregulated, with microRNAs known to be crucial to osteogenesis and disease process such as osteoporosis abnormally expressed. This data demonstrates the impaired functional capacity of BMSCs and their abnormal microRNA expression in patients who suffer a low energy NOF. Future targeted therapies for OP must address this to maximise their restorative effect on diseased bone. The important role microRNAs can play as biomarkers and target sites has been further reinforced

Posterolateral spinal fusion (PSLSF) in rabbits is a challenging model for bone substitutes because the transverse processes are extremely thin and the space to be filled with bone is greater than critical and meiopragic in terms of vascularity. Several investigators have shown beneficial effects of PRP in bone and soft-tissue healing processes. However, controversial results have been reported in clinical setting analysing the effectiveness of PRP. Aim of the present study was to test the effectiveness of PRP in experimental model of PLSF in rabbits. MATERIAL AND METHODS. 20 White females New Zeland Rabbits were used. Seven rabbits (Group 1) had PRP plus carrier on the right side (Group 1A) and plus carrier and fresh bone marrow on the left side (Group 1B). Seven rabbits (Group 2) had carrier alone on the right side (Group 2A) and carrier plus fresh bone marrow on the left side (Group 2B). Six rabbits (Group 3) had sham operation on both right and left sides. Animals were sacrificed 6 months after surgery and the lumbar spine submitted to radiolographic and histologic analysis. Vascular density (VD) was also assessed in the different zone of the grafted material. RESULTS. Radiographs showed a complete fusion in 83% of group 1A and in 83% of group 1B, and in 86% of group 2A and 2B. Pseudarthrosis or non union, was observed in 1 specimen of group 1B and 2A and in all specimens of group 3 (sham). In contrast to radiographic results, no specimen showed a complete bony bridge between the transverse processes on histologic analysis. VD was significantly greater in the periapophyseal compared to the interapophyseal region of the graft material. However, no significant difference was found in the VD between groups. CONCLUSIONS. In this study PRP alone, or augmented with fresh bone marrow, failed to induce a histologically proved bony fusion in the PLSF model. Factors which may influence the effectiveness of PRP should be further addressed before applying PRP in the clinical setting

Nanoscale topography increases the bioactivity of a material and stimulates specific responses (third generation biomaterial properties) at the molecular level upon first generation (bioinert) or second generation (bioresorbable or bioactive) biomaterials. We developed a technique (based upon the effects of nanoscale topography) that facilitated the in vitro expansion of bone graft for subsequent implantation and investigated the optimal conditions for growing new mineralised bone in vitro. Two topographies (nanopits and nanoislands) were embossed into the bioresorbable polymer Polycaprolactone (PCL). Three dimensional cell culture was performed using double-sided embossing of substrates, seeding of both sides, and vertical positioning of substrates. The effect of Hydroxyapatite, and chemical stimulation were also examined. Human bone marrow was harvested from hip arthroplasty patients, the mesenchymal stem cells culture expanded and used for cellular analysis of substrate bioactivity. The cell line specificity and osteogenic behaviour was demonstrated through immunohistochemistry, confirmed by real-time PCR and quantitative PCR. Mineralisation was demonstrated using alizarin red staining. Results showed that the osteoinduction was optimally conferred by the presence of nanotopography, and also by the incorporation of hydroxyapatite (HA) into the PCL. The nanopit topography and HA were both superior to the use of BMP2 in the production of mineralised bone tissue. The protocol from shim production to bone marrow harvesting and vertical cell culture on nanoembossed HaPCL has been shown to be reproducible and potentially applicable to economical larger scale production

Aims

This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients.

In biomaterial engineering the surface of an implant can influence cell differentiation, adhesion and affinity towards the implant. Increased bone marrow derived mesenchymal stromal cell (BMSC) differentiation towards bone forming osteoblasts, on contact with an implant, can improve osteointegration. The process of micropatterning has been shown to improve osteointegration in polymers, but there are few reports surrounding ceramics. The purpose of this study was to establish a co-culture of BMSCs with osteoclast progenitor cells and to observe the response to micropatterned zirconia toughened alumina (ZTA) ceramics with 30 µm diameter pits. The aim was to establish if the pits were specifically bioactive towards osteogenesis or were generally bioactive and would also stimulate osteoclastogenesis that could potentially lead to osteolysis. We demonstrate specific bioactivity of micropits towards osteogenesis with more nodule formation and less osteoclastogenesis. This may have a role when designing ceramic orthopaedic implants

Osteocondritis dissecans (OCD) is a relatively common cause of knee pain. Ideal treatment is still controversial. Aim of this exhibit is to describe the outcomes of 5 different surgical techniques in a series of 63 patients. 63patients (age 22.5±7.4 years) affected by OCD of the femoral condyle (45 medial and 17 lateral) were treated by either osteochondral autologous transplantation, autologous chondrocyte implantation with bone graft, biomimetic nanostructured osteochondral scaffold (Maioregen) implantation, bone-cartilage paste graft or bone marrow derived cells transplantation “one-step” technique. Patient evaluation included IKDC score, eq-vas score, X-Rays and MRI preoperatively and at follow-up. Global mean IKDC improved from pre-operative 40.1±14.6 to 77.2±21.3 (p<0.0005) at mean 5.3±4.7 years follow-up, while eq-vas improved from 51.7±17.0 to 83.5±18.3(p<0.0005). No influence of age, size of the lesion, length of follow-up and associated surgeries on the result was found. No differences were found between the results obtained with different surgeries except a slight tendency of better improvement in the result following autologous chondrocyte implantation (p<0.01). Control MRI evidenced a satisfactory repair of cartilaginous layer and subchondral bone. The techniques described were effective in providing good clinical and radiographic results in the treatment of OCD and confirmed the validity of autologous chondrocyte implantation over time. Newer techniques such as Maioregen implantation and “one-step” base on different rationales, the first relying on the characteristics of the scaffold and the second on the regenerative potential of mesenchymal cells. Both of them have the advantages to be minimally invasive surgeries and to require a single operation

Aims

Osteopetrosis (OP) is a rare hereditary disease that causes reduced bone resorption and increased bone density as a result of osteoclastic function defect. Our aim is to review the difficulties, mid-term follow-up results, and literature encountered during the treatment of OP.

Introduction. Osteochondral defects (OCDs) of the talus are treated initially by arthroscopic bone marrow stimulation. For both large and secondary defects, current alternative treatment methods have disadvantages such as donor site morbidity or two-stage surgery. Demineralized bone matrix (DBM) was published for the treatment of OCDs of rabbit knees. Autologous platelet-rich plasma (PRP) may improve the treatment effect of DBM. We previously developed a goat model to investigate new treatment methods for OCDs of the talus. The aim of the current study was to test whether DBM leads to more bone regeneration than control OCDs, and whether PRP improves the effectiveness of DBM. Methods. A standardized 6-mm OCD was created in 32 ankles of 16 adult Dutch milk goats. According to a randomized schedule, 8 goats were treated with commercially available DBM (Bonus DBM, Biomet BV, Dordrecht, the Netherlands) hydrated with normal saline, and 8 were treated with the same DBM but hydrated with autologous PRP (DBM+PRP). The contralateral ankles (left or right) were left untreated and served as a control. The goats were sacrificed after 24 weeks and the tali were excised. The articular talar surfaces were assessed macroscopically using the international cartilage repair society (ICRS) cartilage repair assessment, with a maximum score of 12. Histologic analysis was performed using 5-μm sections, and histomorphometric parameters (bone% and osteoid%) were quantified on representative areas of the surface, center, and peripheral areas of the OCDs. Furthermore, μCT-scans of the excised tali were obtained, quantifying the bone volume fraction, trabecular number, trabecular thickness, and trabecular spacing in both the complete OCDs and the central 3-mm cylinders. Results. All goats recovered well and were able to bear full weight within 24 hours after surgery. The mean ICRS-score of the ankles treated with DBM was 8.0 ± 1.0, compared to a score of 8.4 ± 1.5 in the contralateral ankle (NS); those treated with DBM+PRP scored 6.9 ± 2.4, compared to 7.4 ± 2.0 in the contralateral ankle (NS). Histologic analysis showed four different patterns of healing, distributed evenly over the treatment and control groups: type 1 (n = 4), almost completely healed; type 2 (n = 11), restoration of the subchondral bone with a cystic lesion underneath; type 3 (n = 14), superficial defect with regeneration from the margins and bottom; type 4 (n = 3), no healing tendency. Histomorphometry and μCT revealed no statistically significant difference between treatment (DBM or DBM+PRP) and contralateral control or between both treatment groups in any of the parameters investigated. Conclusion. No treatment effect of DBM was found compared to control defects, and the addition of PRP was not beneficial

Introduction. The combined incubation of a composite scaffold with bone marrow stromal cells in a perfusion bioreactor could make up a novel hybrid graft material with optimal properties for early fixation of implant to bone. The aim of this study was to create a bioreactor activated graft (BAG) material, which could induce early implant fixation similar to that of allograft. Two porous scaffold materials incubated with cells in a perfusion bioreactor were tested in this study. Methods and Materials. Two groups of 8 skeletally mature female sheep were anaesthetized before aspiration of bone marrow from the iliac crest. For both groups, mononuclear cells were isolated, and injected into a perfusion bioreactor (Millenium Biologix AG, Switzerland). Scaffold granules Ø∼900–1500 μm, ∼88% porosity) in group 1, consisted of hydroxyapatite (HA, 70%) with -tricalcium-phosphate (−TCP, 30%) (Danish Technological Institute, Denmark). The granules were coated with poly-lactic acid (PLA) 12%, in order to increase the mechanical strength of the material (Phusis, France). Scaffold granules Ø∼900–1400 μm, 80% porosity) in group 2 consisted of pure HA/-TCP (Fin Ceramica, Italy). For both groups, cells were incubated in the bioreactor for 2 weeks. Fresh culture medium supplemented with dexamethasone and ascorbic-acid was added every third or fourth day. Porous titanium alloy implants with diameter=length=10mm (Biomet, USA) were inserted bilaterally in each of the distal femurs of the sheep; thus 4 implants in each sheep. The concentric gap (2 mm) surrounding the implant was filled with 1) BAG (autogenous), 2) granules, 3) granules+bone marrow aspirate (BMA, autologous) or 4) allograft. The sheep were euthanized after 6 weeks. Distal femurs were removed and implant-bone samples were divided in two parts. The superficial part was used for mechanical testing and micro-CT scanning, and the profound part for histomorphometry. Push-out tests were performed on an 858 Bionix MTS hydraulic materials testing machine. Shear mechanical properties between implant and newly generated bone were calculated to assess implant fixation. Results were assessed by One-way ANOVA. P-values less than 0.05 were considered significant. Results. One sheep in group 1 had to be euthanized after 4 weeks (excluded). One implant in each group was loosened and could not undergo push-out test (excluded). Group 1: No significant differences regarding failure energy (kJ/m2, p=0.44) or ultimate shear strength (MPa, p=0.17) could be seen. Shear stiffness (MPa) was significantly higher for the allograft group (p=0.04). Group 2: No significant differences regarding failure energy (p=0.11) or shear stiffness (p=0.52) could be seen. Ultimate shear strength was significantly higher for allograft (p=0.04). Results from μ-CT scanning and histomorphometry are pending. Discussion and Conclusion. The present study shows a possible effect of bioreactor activated bone substitute on early implant fixation. We are currently working on bone microarchitecture surrounding implant and histomorphometry. These results will aid in determining if BAG could make up a promising alternative for allograft as bone graft material

Aims

Dual plating of distal femoral fractures with medial and lateral implants has been performed to improve construct mechanics and alignment, in cases where isolated lateral plating would be insufficient. This may potentially compromise vascularity, paradoxically impairing healing. This study investigates effects of single versus dual plating on distal femoral vascularity.

Objectives

The aim of this systematic literature review was to assess the clinical level of evidence of commercially available demineralised bone matrix (DBM) products for their use in trauma and orthopaedic related surgery.

Objectives

Bisphosphonates are widely used as first-line treatment for primary and secondary prevention of fragility fractures. Whilst they have proved effective in this role, there is growing concern over their long-term use, with much evidence linking bisphosphonate-related suppression of bone remodelling to an increased risk of atypical subtrochanteric fractures of the femur (AFFs). The objective of this article is to review this evidence, while presenting the current available strategies for the management of AFFs.

Objectives

Nonunion is one of the most troublesome complications to treat in orthopaedics. Former authors believed that atrophic nonunion occurred as a result of lack of mesenchymal stem cells (MSCs). We evaluated the number and viability of MSCs in site of atrophic nonunion compared with those in iliac crest.

Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks.

In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites.