Introduction. In osteonecrosis of the femoral head (ONFH), progression of collapse is influenced by a repair reaction, especially bone resorptive activity, around the necrotic bone. Alendronate is a potent inhibitor of bone resorption by inhibiting osteoclast activity. We performed a clinical study to test if systemic alendronate treatment would prevent the development of collapse in patients with ONFH. Methods. Thirty-three hips in 22 ONFH patients with initial ARCO Stage 1 to 3 were included. Fourteen patients (20 hips) received daily administration of oral alendronate 5mg/day (alendronate group) and 8 patients (13 hips) did not receive alendronate administration (Control group). Baseline investigations included anteroposterior and lateral plain radiographs, T1-weighted magnetic resonance imaging (MRI), and biochemical markers (urinary NTX and serum BAP). Examination of the biochemical markers were repeated at 3, 6, and 12 months, and MRI imaging was repeated at 12 months. At 3 years, clinical symptoms and findings on plain radiographs were compared between the 2 groups. Advancement of ARCO stages or increase of collapse by more than 2 mm were considered as development of collapse. Results. At baseline, there were no significant differences regarding patients' age, distribution of gender, etiology, ARCO radiographic stage, and extent of necrosis between the 2 groups. In the alendronate group, there was an early decrease of osteoclast activity (NTX) and osteoblastic activity (BAP) at 3 months, with significantly larger decrease in NTX (43%) than BAP (21%) at 12 months. At 3 years, development of collapse was observed in 7 hips (54%) of the Control group, and in 3 hips (15%) of the alendronate group. Hip pain was noted in 9 hips (69%) of the Control group, and in 6 hips (30%) of the alendronate group. There was a significant difference oncollapse development and occurrence of hip pain between the two groups (p<0.05). Signal change around the necrotic region on serial MRI images during the first 1 year was observed in 54 % of the Control group, and only 11% of the alendronate group. Conclusion. Alendronate therapy decreased biochemical markers, especially osteoclast activity, after an early period from start of administration. Several clinical studies have shown promising short-term results for prevention of collapse in ONFH by administration of bisphosphonates. The present study showed a significant preventing effect of collapse development by administration of alendronate which was maintained for 3 years of treatment. Low incidence of signal change on serial MRI images may also reflect decrease of repair activity in the alendronate group. Further studies with longer follow-up, larger numbers of patients, and randomized administration of the drug among patients are required., However, alendronate administration may become one of the effective conservative treatments which might obviate the need for osteotomy or replacement surgery in some populations of ONFH patients

We investigated the effect of locally administered bisphosphonate on distraction osteogenesis in a rabbit model and evaluated its systemic effect. An osteotomy on the right tibia followed by distraction for four weeks was performed on 47 immature rabbits. They were divided into seven equal groups, with each group receiving a different treatment regime. Saline and three types of dosage of alendronate (low, 0.75 μg/kg; mid, 7.5 μg/kg and high 75 μg/kg) were given by systemic injection in four groups, and saline and two dosages (low and mild) were delivered by local injection to the distraction gap in the remaining three groups. The injections were performed five times weekly during the period of distraction. After nine weeks the animals were killed and image analysis and mechanical testing were performed on the distracted right tibiae and the left tibiae which served as a control group. The local low-dose alendronate group showed a mean increase in bone mineral density of 124.3 mg/cm. 3. over the local saline group (analysis of variance, p < 0.05) without any adverse effect on the left control tibiae. The findings indicate that the administration of local low-dose alendronate could be an effective pharmacological means of improving bone formation in distraction osteogenesis

Introduction. Osteonecrosis (ON) is one of the most debilitating skeletal disorders. Most patients with ON of the femoral head eventually require surgery, usually total hip arthroplasty, within a few years of disease onset. Previous reports have shown that alendronate reduces osteoclastic activity and reduces the incidence of femoral head collapse in osteonecrotic hips. A randomized study to examine the ability of alendronate to delay or prevent femoral head collapse was performed. Methods. From June 2005 to December 2006, sixty four patients were enrolled and randomly assigned to alendronate or placebo. Five patients were excluded from the analysis because of their failure to adhere to the study protocol. Disease progression was evaluated using radiographs and magnetic resonance imaging (MRI). Results. While the proportion of patients in the alendronate group who underwent total hip arthroplasty was 13% (4 of 31 patients), the proportion of patients undergoing the procedure in the placebo group was 29% (8 of 28 patients; p=0.22, cumulative incidence between the two groups by log-rank test). As such, there was a numerical reduction in the rate of total hip arthroplasty in the alendronate group compared to placebo that did not achieve statistical significance likely because the study was originally powered to detect a between-group difference based on event rates of 35.7% and 3.4% in the placebo and alendronate groups, respectively. Conclusion. Alendronate treatment shows promise for the treatment of atraumatic osteonecrosis. However, additional studies are needed to confirm our results. Osteotomy or bone grafting still remains the procedure of choice for osteonecrosis of the femoral head prior to collapse. Disclosure. The study was supported in part by Merck Sharp & Dohme (I.A) Corp. Taiwan Branch. All these schools received some financial reimbursement for the study

Bone healing especially in elderly patients is a complex process with limited therapeutic options. In recent years the use of BMP2 for fracture healing is investigated extensively. However, for many applications superficial amounts of BMP2 were required for efficacy due to the absence of sustained release carriers and severe side effects have reported thereby limiting the use of BMP2. Here we present an alternative method based on the use of a combination of low molecular weight compounds, testosterone and alendronate, with established safety profiles in men. Moreover, in contrast to BMP2 which activates both osteoblasts and osteoclasts, this combination of drugs enhances osteoblast activity but simultaneously inhibits osteoclast activity resulting in a net effect of bone growth. Human primary osteoblasts were obtained from bone of patients requiring knee prostheses and cultured in the presence of various concentrations testosterone with and without alendronate. Optimal concentrations were selected and used to stimulate 5×8 mm porcine bone biopsies for 4 weeks. Medium was exchanged regularly and ALP activity was determined. At endpoint biopsies were analyzed in a MicroCT (Bruker Skyscan 1076) to analyze bone volume (BV), trabecular thickness (Tb.Th) and tissue volume (TV). Bone strength was measured using Hounsfield (H10KT) test equipment. The data obtained showed a significant and dose dependent increase in ALP activity of primary osteoblasts (day 7–10) indicating robust activation of osteoblast activity. Optimal and synergistic ALP activation was observed when treating cells with 15–375 nM testosterone in combination with 2 μM alendronate. Significant inhibition (75%) of osteoclast activity was observed by alendronate (2–10 μM) which was further enhanced by high testosterone levels. This concept was further tested in bovine bone biopsies cultured for 4 weeks in the presence of 75 nM testosterone and 2 μM alendronate. MicroCT analysis of the biopsies revealed a ± 40% increase in both bone volume (trabecular and cortical bone) and bone strength. Moreover bone mineral density was increased by 20% indicating increased mineralization of bone tissue. Treatment of human primary osteoblasts or human or bovine bone explants with a combination of an androgen (testosterone) and a bisphosphonate (alendronate) significantly enhance bone growth and bone mineral density. Moreover, bone strength was increased indicating the formation of high quality bone tissue. These findings are the basis for the development of sustained release materials to be applied locally at the bone fracture site, which would allow for low amounts of the drugs and no systemic exposure. By encapsulating testosterone and alendronate in a biodegradable polymer coating, a sustained release up to 5 weeks can be achieved, and the loaded coating can be applied in combination with collagen membranes to improve bone healing or as a coating onto implants to improve osseo-integration

Soaking bone grafts in a bisphosphonate solution before implantation can prevent their resorption and increase the local bone density in rats and humans. However, recent studies suggest that pre-treatment of allografts with bisphosphonate can prevent bone ingrowth into impaction grafts. We tested the hypothesis that excessive amounts of bisphosphonate would also cause a negative response in less dense grafts. We used a model where non-impacted metaphyseal bone grafts were randomised into three groups with either no bisphosphonate, alendronate followed by rinsing, and alendronate without subsequent rinsing, and inserted into bone chambers in rats. The specimens were evaluated histologically at one week, and by histomorphometry and radiology at four weeks. At four weeks, both bisphosphonate groups showed an increase in the total bone content, increased newly formed bone, and higher radiodensity than the controls. In spite of being implanted in a chamber with a limited opportunity to diffuse, even an excessive amount of bisphosphonate improved the outcome. We suggest that the negative results seen by others could be due to the combination of densely compacted bone and a bisphosphonate. We suggest that bisphosphonates are likely to have a negative influence where resorption is a prerequisite to create space for new bone ingrowth

A painful “dreaded black line” (DBL) has been associated with progression to complete fractures in atypical femur fractures (AFF). Adjacent sclerosis, an unrecognized radiological finding, has been observed in relation to the DBL. We document its incidence, associated features, demographics and clinical progression. We reviewed plain radiographs of 109 incomplete AFFs between November 2006 and June 2021 for the presence of sclerosis adjacent to a DBL. Radiographs were reviewed for location of lesions, and presence of focal endosteal or periosteal thickening. We collected demographical data, type and duration of bisphosphonate therapy, and progression to fracture or need for prophylactic stabilization, with a 100% follow up of 72 months (8 – 184 months). 109 femurs in 86 patients were reviewed. Seventeen sclerotic DBLs were observed in 14 patients (3 bilateral), involving 15.6% of all femora and 29.8% of femora with DBLs. Location was mainly subtrochanteric (41.2%), proximal diaphyseal (35.3%) and mid-diaphyseal (23.5%), and were associated with endosteal or periosteal thickening. All patients were female, mostly Chinese (92.9%), with a mean age of 69 years. 12 patients (85.7%) had a history of alendronate therapy, and the remaining 2 patients had zoledronate and denosumab therapy respectively. Mean duration of bisphosphonate therapy was 62 months. 4 femora (23.5%) progressed to complete fractures that were surgically managed, whilst 6 femora (35.3%) required prophylactic fixation. Peri-lesional sclerosis in DBL is a new radiological finding in AFFs, predominantly found in the proximal half of the femur, at times bilateral, and are always associated with endosteal or periosteal thickening. As a high proportion of patients required surgical intervention, these lesions could suggest non-union of AFFs, similar to the sclerotic margins commonly seen in fractures with non-union. The recognition of and further research into this new feature could shed more light on the pathophysiological progression of AFFs

Summary Statement. This work proved by prospective clinical and radiological controlled study that the best regimen for treatment of early KOA is combination of NSAIDS, physiotherapy, vasoprotective and vasodilator drugs, and alendronate. Introduction. There is controversy in the literatures regarding the best treatment for early knee osteoarthritis because there is a more controversy regarding the initiating factor of KOA The Objectives of this work were to evaluate the efficacy of various treatment regimens for the prevention of progression of early knee osteoarthritis (KOA). Also, to elucidate the factors for initiation and progression of KOA. Patients and Methods. Four groups of 50 patients with early KOA were treated with four treatment regimens. The first group (control) received analgesics as needed for one year. The second group received non steroidal anti-inflammatory drugs (NSAIDS) plus physiotherapy for one month; with analgesics as needed for the rest of the year. The third group received NSAIDS plus physiotherapy, plus vasoprotective and vasodilator drugs for one month; vasoprotective and vasodilator drugs for the next six months, and analgesics as needed for the rest of the year. The fourth group received NSAIDS plus physiotherapy, plus vasoprotective and vasodilator drugs plus alendronate for one month; vasoprotective and vasodilator drugs plus alendronate for the next six months; and analgesics as needed for the rest of the year. The age of the patients was from 40 to45years. There were 25 males and 25 females in each group. Patients with causes of secondary KOA (e.g. rheumatoid, gouty, traumatic, etc.) were excluded. All patients were subjected to Pre- and post treatment regimens clinical and radiological evaluation Clinical evaluation included history of progressive knee pain for 3–6weeks, limping, Visual analog pain score, tenderness, and knee range of motion. Radiological evaluation included 1.0 T MRI which was performed using proton density-weighted, fat-suppressed sequences. BML size and cartilage status were scored in the same sub regions according to the WORMS system. Results. Progression of KOA in the first, second, third, and fourth group were 66%, 55%, 25%, and 19% of patients respectively No sex difference was detected. Conclusion. The best treatment regimen for early KOA is combination of NSAIDS, physiotherapy, vasoprotective and vasodilator drugs, and alendronate. Vascular and local osteoporotic factors may play a major role in progression of KOA

Osteoarthritis (OA) is a joint degenerative disease leading to chronic pain and disability, thus resulting in a major socioeconomic health burden. OA, which has long been believed to be a cartilage disease, is now considered a whole-joint disorder affecting various anatomical structures, including subchondral bone. Hyaluronic Acid (HA) is commonly used as intra-articular viscosupplementation therapy for its mechanical features and biological effects. Bisphosphonates (BPs) are antiresorptive agents inhibiting recruitment and maturation of osteoclast precursors and activity of mature osteoclasts in the bone. Pre-clinical evidences in the literature, show that intra-articular BPs could impact on OA progression, slowing down or reversing it. The combination of HA biological and mechanical role and Alendronate (ALD) antiresorptive effect could be an interesting strategy for OA treatment. This study describes the synthesis and characterization of FID-134, a new chemical derivative of HA conjugated with ALD by means of a covalent bond, cleavable in physiological condition. FID-134 was synthesized starting from 500 kDa HA: chemical structure and functionalization degree with ALD were investigated by NMR and ICP-OES. Kinetics of ALD release from FID-134 was determined in TRIS buffer at 37°C and compared to a simple mixture of HA+ALD. 20mg/mL formulations of FID-134 and HA+ALD were investigated for viscoelastic properties, in absence and presence of Ca. 2+. ions. The cytotoxicity of FID-134 and free ALD were tested on Saos-2 osteoblasts (ATCC HTB-85) and on primary bovine chondrocytes (PBC) at day 1, 3 and 7. The efficacy of FID-134 was assessed in an inflammatory arthritis in vitro model, where bovine cartilage biopsies were exposed to IL-1β/OSM (10ng/mL) for 3 weeks; at the same time, cartilage explants were treated with FID-134. Collagen release in the surnatants was quantified and compared to controls. FID-134 structure was confirmed by NMR and the 20% mol/mol functionalization degree was determined by ICP-OES. Only about 50% of total bound ALD was released from FID-134 within 7 days, resulting slower compared to HA+ALD mixture. In presence of Ca. 2+. ions, viscoelastic properties of FID-134 dramatically improved, while HA+ALD formulation remained unaffected. The cytotoxicity of ALD was evident at 100 μM on Saos-2 and PBC after 3 days, while no cytotoxicity was observed at 7 days with FID-134. In the cartilage explant model, a strong collagen release was detected in inflammatory conditions after 3 weeks; this tendency was reversed, and collagen release halved when FID-134 was added to the biopsies. The synthesized HA-ALD adduct, FID-134, opens the door for a new approach for OA treatment. The results suggest that FID-134 could be beneficial in cartilage degradation and in restoration of subchondral bone function. Finally, local administration and controlled BP release would likely overcome the drawbacks of ALD oral administration, such as unspecific features and long-term toxic side effects

The superior analgesic effects of minodronate compared with other bisphosphonates has been previously reported. However, to our knowledge, there are no studies analyzing the analgesic effects of bisphosphonates on chronic pain. The purpose of the present study was to evaluate the analgesic effects of minodronate (MIN), alendronate (ALN), and pregabalin (PRG) on chronic pain caused by chronic constriction injury (CCI) of the sciatic nerve. Four-week-old female Wister rats underwent ovariectomy. At 8 weeks old, the left sciatic nerve was ligated to induce the chronic pain model (CCI side), and sham surgery was performed on the right posterior limb as a CCI control (control side). The rats were divided into the following four groups: 1) MIN group, administered with minodronate (0.15 mg/kg/week) (n = 10); 2) ALN group, administered with alendronate (0.15 mg/kg/week) (n = 10); 3) PRG group, administered with pregabalin (10 mg/kg) (n = 9); and 4) Control group, administered with vehicle (n = 10). Treatments were administered subcutaneously every week for 2 weeks immediately after CCI. To quantify the sensitivity to a tactile stimulus, paw withdrawal in response to a tactile stimulus was measured using von Frey filaments at 0, 1, and 2 weeks after CCI. Von Frey filaments were applied to the plantar surface of the hindpaws for 3 s, and this was repeated three times. Paw withdrawal in response to the stimulus was evaluated by scoring as follows: 0, no response; 1, a slow and/ or slight response to the stimulus; 2, a quick withdrawal response; 3, an intense withdrawal response away from the stimulus. The mean value of the score was adopted as the pain score. After evaluating the response, bilateral femurs were harvested for bone mineral density (BMD) measurements. The pain score of the CCI side was significantly higher than that of the sham side in all groups (p < 0.05) at each time point. The pain score for the MIN group, but not the ALN group, of the CCI side was significantly lower (p = 0.05) at 0 and 1 week after CCI. Total femoral BMD of the CCI side was significantly lower in the PRG and Control groups than those of the MIN and ALN groups (p < 0.05). No significant difference was identified for BMD between the MIN and ALN groups. Minodronate showed a significant analgesic effect on chronic pain and suppressed osteoporotic changes caused by CCI

Summary Statement. In this study it has been considered an alternative therapeutic approach to bone resorption diseases by using plant decoctions to improve adherence from patients to the treatment. In this context, Hemidesmus indicus represents a possible therapeutic or adjuvant natural compound. Introduction. The acceleration of bone remodelling, with an excessive osteoclastogenesis or activation of mature osteoclasts, causes the loss of bone mass which is implicated in bone resorption diseases. Conventional therapies are expensive and limited by systemic toxicity and low drug bioavailability. Alternative treatments that are not only effective but also administered employing formulations and dosages different from conventional ones, may improve adherence to therapy, having a positive influence on clinical outcomes. Experimental evidence have attributed antiproliferative and apoptosis inducing activity on different cell lines (including osteoclast precursors or mature osteoclasts) to four plants used in Ayurvedic medicine: Asparagus racemosus (AR), Emblica officinalis (EO), Hemidesmus indicus (HI) and Rubia cordifolia (RC) These properties could be helpful in the treatment of some bone resorption diseases. In order to clarify the possible therapeutic effects of these compounds, the anti-osteoclast activity of their decoctions were evaluated. Methods. The anti-osteoclast activity of natural compounds was evaluated on primary cultures of human osteoclasts generated by isolating peripheral blood monocytes from buffy coat and treating cells with medium supplemented with differentiating factors. To evaluate the effect on osteoclastogenesis, osteoclast precursors were treated with different concentrations of plant decoctions and characterised by the formation of multinucleated cells and the expression of tartrate-resistant acid phosphatase. To evaluate the osteoclasts apoptosis inducing activity mature osteoclasts were treated with the compounds and stained with Hoechst 33258, to make clear the possible nuclear pyknosis, and phalloidin-TRITC to highlight the structure of the typical osteoclast actin ring. The toxicity of compounds on osteogenic precursors was evaluated by the Alamar Blue assay after 7 days of cells treatment with bioactive concentrations of decoctions. Results. At the higher concentrations, all the decoctions had inhibited osteoclastogenesis with an effect similar to that of alendronate (positive control), but only HI was effective like alendronate at lower concentrations. The percentage of apoptotic osteoclasts was very low in control cultures (30 ± 2%), but increased significantly when cells were exposed to the highest concentration of EO (P < 0.001), HI (P < 0.001), and RC (P < 0.05). It was not observed the same effect when cells were exposed to the highest concentration of AR. At the highest concentrations AR has completely inhibited the proliferation of osteogenic precursors, EO was toxic at all tested concentrations, while RC was toxic only at the highest ones. On the contrary, HI showed absence of toxicity on osteogenic precursors at all tested concentrations. Conclusion. An ideal anti-resorption drug should exert an anti-osteoclastic activity without interfering with the proliferative capacity of osteogenic precursors. For these reasons, among all the plants evaluated in this study, HI represents a possible therapeutic candidate. In fact, it demonstrated the greater effectiveness of anti-osteoclast activity, both in terms of inhibition of osteoclastogenesis that induction of apoptosis, but showed no toxicity on osteogenic precursors

Little is known on how sensory nerves and osteoclasts affect degenerative processes in subchondral bone in osteoarthritis (OA). Substance P (SP) effects on bone are ambivalent but physiological levels are critical for proper bone quality whereas α-calcitonin gene-related peptide (αCGRP) has anabolic effects. Here, we aimed to analyse the influence of an altered sensory neuropeptide microenvironment on subchondral bone in murine OA. Transection of the medial meniscotibial ligament (DMM) of the right hind leg induced joint instability leading to development of OA. Subchondral bone of tibiae from wildtype (WT), alendronate-treated WT (ALN, osteoclast inhibition), αCGRP- and SP- (Tachykinin (Tac)1) knockout mice was analysed by micro-computed tomography 4 and 12 weeks after DMM or sham surgery. Bone resorption marker CTX-I was measured in serum. We observed osteophytosis in all DMM groups and ALN sham mice 4 weeks after surgery but also in sham groups 12 weeks after surgery. In subchondral bone, bone volume density (BV/TV) increased from 4 to 12 weeks after surgery in DMM WT and Tac1-/− mice. DMM WT mice additionally had increased trabecular numbers (Tb.N.) and decreased trabecular space (Tb.Sp.) over time. Sham mice also showed time-dependent alterations in subchondral bone. In sham WT and αCGRP-/− mice specific bone surface (BS/BV) decreased and trabecular thickness (Tb.Th.) increased from 4 to 12 weeks after surgery while subchondral BV/TV of αCGRP-/− mice increased. Comparison of subchondral bone parameters at each time point showed elevated BV/TV in ALN DMM compared to WT DMM mice 4 weeks after surgery. In addition, both ALN sham and DMM mice showed a reduced BS/BV compared to WT. 4 weeks after sham surgery Tb.Th. was highest in ALN mice. In DMM WT mice Tb.Sp. was higher compared to ALN and αCGRP-/−. 12 weeks after surgery (late OA stage), BS/BV of ALN sham mice was significantly reduced in relation to ALN DMM, WT and Tac1-/− sham, while Tb.Th. increased compared to WT. DMM significantly decreased Tb.N. and increased Tb.Sp. in Tac1-/− compared to sham 12 weeks after surgery. CTX-I concentrations were significantly higher in ALN compared to Tac1-/− mice 4 weeks after sham surgery. 12 weeks after sham surgery CTX-I concentrations of WT mice were increased compared to αCGRP-/− and Tac1-/− mice. Over time, DMM induced stronger changes in subchondral bone of WT mice compared to knockout strains. WT and αCGRP-/− sham mice also show alterations in bone parameters over time indicating age-related effects on bone structure. SP deficiency enhanced DMM-induced structural bone alterations in late stage OA emphasizing the importance of SP under pathophysiological conditions. Osteoclast inhibition with alendronate proved to be preservative for time-dependent changes of subchondral bone observed in both, DMM and sham mice. Interestingly, ALN treatment did not reduce bone turnover marker CTX-I, and additionally promoted early osteophyte formation in sham mice

Osteoporosis is a global health issue with 200 million people suffering worldwide and it is a common condition in the elderly. Bisphosphonates including alendronate and risendronate are considered as the first line treatment for osteoporosis. However, there is increasing evidence that bisphosphonate (BP) therapy is associated with atypical fractures. Animal studies have reported a dose-dependent association between the duration of BP therapy and the accumulation of micro-damage. We tested the hypothesis that hip fracture patients treated with BP exhibited greater micro-damage density than untreated fracture and ‘healthy’ aging non-fracture controls. Trabecular bone cores from patients treated with BP were compared with patients who had not received any treatment for bone metabolic disease (ethics reference: R13004). Non-fractured cadaveric femora from individuals with no history of bone metabolic disease were used as controls. Cores were imaged in high spatial resolution (∼1.3µm) using Synchrotron X-ray tomography (Diamond Light Source Ltd.) A novel classification system was devised to characterise features of micro-damage in the Synchrotron images: micro-cracks, diffuse damage and perforations. Synchrotron micro-CT stacks were visualised and analysed using ImageJ, Avizo and VGStudio MAX. Our findings show that the BP group had the highest micro-damage density across all groups. The BP group (7.7/mm. 3. ) also exhibited greater micro-crack density than the fracture (4.3/mm. 3. ) and non-fracture (4.1/mm. 3. ) controls. Furthermore, the BP group (1.9/mm. 3. ) demonstrated increased diffuse damage when compared to the fracture (0.3/mm. 3. ) and non-fracture (0.8/mm. 3. ) controls. In contrast, the BP group (1.9mm. 3. ) had fewer perforations than fracture (3.0/mm. 3. ) and non-fracture controls (3.9/mm. 3. ). BP inhibits bone remodelling, thereby reducing the number of perforated trabeculae, but over-suppression leads to micro-damage accumulation. Accumulated damage could weaken the trabecular bone in the femoral head and neck, increasing the risk of a fracture during a trip or fall

Objectives

Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis.

Objectives

Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls.

In an attempt to increase the life of cementless prostheses, an hydroxyapatite-coated implant which releases a bisphosphonate has been suggested as a drug-delivery system. Our in vitro study was designed to determine the maximum dose to which osteoblasts could be safely exposed.

Our findings demonstrated that zoledronate did not impair the proliferation of human osteoblasts when used at concentrations below 1 μm. Murine cells can be exposed to concentrations as high as 10 μm.

A concentration of 0.01% of titanium particles did not impair the proliferation of either cell line. Zoledronate affected the alkaline phosphatase activity of murine osteoblasts through a chelation phenomenon. The presence of titanium particles strongly decreased the alkaline phosphatase activity of murine osteoblasts. We did not detect any synergic effect of zoledronate and titanium particles on the behaviour of both human and murine osteoblasts.

Objectives

To assess the sensitivity and specificity of self-reported osteoporosis compared with dual energy X-ray absorptiometry (DXA) defined osteoporosis, and to describe medication use among participants with the condition.