Received Bisphosphonate Treatment Research Articles

Demographics and medical burden of osteogenesis imperfecta: a nationwide database analysis.

This study examines osteogenesis imperfecta, a hereditary connective tissue disorder causing pediatric fractures and limb deformities, using a nationwide database from Taiwan to analyze clinical features and medical burden. The study identified validated OI patients from the Catastrophic Illness Registry in the National Health Insurance Research Database from 2008 to 2019. Demographic data and medical resource utilization were analyzed. A multivariate Cox model assessed the influence of sex, validation age, and comorbidities. 319 OI patients (M/F = 153/166) were identified, with 58% validated before age 20. Prevalence and incidence were 0.8-1.3/100,000 and 0.02-0.09/100,000, respectively, with higher rates in the pediatric demographic. In the study period, 69.6% of the patients had admission history, primarily to pediatric and orthopedic wards. The median admission number was 3, with a median length of stay of 12days and a median inpatient cost of approximately 3,163 USD during the period. Lower limb fractures were the main reason for hospitalization. 57% of OI patients received bisphosphonate treatment. The leading causes of mortality were OI-related deaths, neurovascular disease, and cardiovascular disease. The median age of validation in the non-survival group was significantly higher compared to the survival group (33 vs. 14years), and patients validated during childhood required more inpatient fracture surgeries than those validated during adulthood. This study provides comprehensive real-world evidence on the clinical characteristics and high medical resource utilization of OI patients in a low prevalence region like Taiwan. Early diagnosis is crucial for improving care quality and enhancing health outcomes.

Bisphosphonate therapy in the management of diffuse sclerosing osteomyelitis of the mandible: a systematic review and narrative synthesis

Background: Diffuse sclerosing osteomyelitis (DSO) affecting the mandible is an uncommon condition characterised by recurrent pain and functional disturbances. Traditional treatments involving antibiotics, steroids, and analgesics have generally yielded unsatisfactory results. Numerous articles have proposed the utilisation of bisphosphonate therapy as an alternative approach to achieve sustained symptom relief. This study aims to consolidate the available evidence on the effectiveness of bisphosphonate therapy in managing DSO. Methods: A systematic review protocol was registered with PROSPERO and reported in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses. Comprehensive electronic search strategies were devised, and studies were screened based on predefined inclusion and exclusion criteria. Results: Ten articles met the eligibility criteria, encompassing a total of 135 patients diagnosed with DSO who received bisphosphonate treatment. All included studies consistently reported a reduction in pain levels and swelling, along with a decrease in the cumulative use of analgesics. The majority of patients reported long-lasting symptom improvement with bisphosphonate therapy. Notably, four studies documented improvements in maximal mouth opening, with one study reporting a mean increase of 9.6mm. Furthermore, six studies observed improvements in panoramic radiographs and cone beam computed tomography scans, with one publication describing two patients exhibiting near-normal bone architecture. Importantly, all studies reported the absence of long-term complications. Conclusions: Bisphosphonate therapy emerges as a promising treatment modality for DSO, exhibiting efficacy in symptom alleviation and radiological enhancement while conferring lasting benefits. Nevertheless, further prospective studies are warranted to refine treatment protocols and substantiate these findings.

PLS3 Mutations in X-Linked Osteoporosis: Clinical and Genetic Features in Five New Families.

Childhood-onset osteoporosis is a rare but clinically significant condition. Studies have shown pathogenic variants in more than 20 different genes as causative for childhood-onset primary osteoporosis. The X-chromosomal PLS3, encoding Plastin-3, is one of the more recently identified genes. In this study, we describe five new families from four different European countries with PLS3-related skeletal fragility. The index cases were all hemizygous males presenting with long bone and vertebral body compression fractures. All patients had low lumbar spine bone mineral density (BMD). The age at the first clinical fracture ranged from 1.5 to 13 years old. Three of the identified PLS3 variants were stop-gain variants and two were deletions involving either a part or all exons of the gene. In four families the variant was inherited from the mother. All heterozygous women reported here had normal BMD and no bone fractures. Four patients received bisphosphonate treatment with good results, showing a lumbar spine BMD increment and vertebral body reshaping after 10months to 2years of treatment. Our findings expand the genetic spectrum of PLS3-related osteoporosis. Our report also shows that early treatment with bisphosphonates may influence the disease course and reduce the progression of osteoporosis, highlighting the importance of early diagnosis for prompt intervention and appropriate genetic counseling.

Bisphosphonates and Their Connection to Dental Procedures: Exploring Bisphosphonate-Related Osteonecrosis of the Jaws.

Bisphosphonates are widely used to treat osteoporosis and malignant tumors due to their effectiveness in increasing bone density and inhibiting bone resorption. However, their association with bisphosphonate-related osteonecrosis of the jaws (BRONJ) following invasive dental procedures poses a significant challenge. This review explores the functions, mechanisms, and side effects of bisphosphonates, emphasizing their impact on dental procedures. Dental patients receiving bisphosphonate treatment are at higher risk of BRONJ, necessitating dentists' awareness of these risks. Topical bisphosphonate applications enhance dental implant success, by promoting osseointegration and preventing osteoclast apoptosis, and is effective in periodontal treatment. Yet, systemic administration (intravenous or intraoral) significantly increases the risk of BRONJ following dental procedures, particularly in inflamed conditions. Prevention and management of BRONJ involve maintaining oral health, considering alternative treatments, and careful pre-operative and post-operative follow-ups. Future research could focus on finding bisphosphonate alternatives with fewer side effects or developing combinations that reduce BRONJ risk. This review underscores the need for further exploration of bisphosphonates and their implications in dental procedures.

891 A Systematic Review and Narrative Synthesis on the Efficacy of Bisphosphonate Therapy in the Management of Diffuse Sclerosing Osteomyelitis

Abstract Aim Diffuse Sclerosing Osteomyelitis (DSO) of the mandible is a rare condition, characterised by recurrent severe pain, and functional disturbances such as trismus. Management of DSO through antibiotics, steroids, and analgesia has been generally unsatisfactory. Several articles have suggested the use of bisphosphonate therapy as an alternative treatment option to achieve long-lasting symptom improvement. We aim to summarise all evidence relating to the efficacy of bisphosphonate therapy in DSO. Method A systematic review protocol was registered with PROSPERO and reported in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses. Comprehensive electronic search strategies of six databases were developed. Studies were screened according to the inclusion and exclusion criteria by two independent reviewers. Results Eight articles were eligible for inclusion. A total of 102 patients with a confirmed diagnosis of DSO received bisphosphonate treatment following a trial of conservative management. All studies reported significant reduction in levels of pain and swelling, and a reduction in cumulative doses of analgesics. Majority of patients reported that bisphosphonate therapy provided long-lasting symptom improvement. Three studies reported improvements in maximal mouth opening, with one study reporting a mean increase of 9.6mm. Improvements in panoramic radiographs and cone beam CT scans were also observed in five studies, with four patients demonstrating almost normal-to-normal bone architecture. Finally, all studies reported no long-term complications. Conclusions Bisphosphonate therapy does appear to be a promising treatment option for DSO. It has shown to improve symptoms and radiological features, providing long-term benefits. Further prospective studies are required to finetune treatment protocols.

Fracture risk after deprescription of bisphosphonates: Application of real-world data in primary care

PurposeTo compare the effect of discontinuing bisphosphonate treatment on fracture risk in postmenopausal women at high versus low risk of fracture. DesignRetrospective, longitudinal and population-based cohort study. SettingBarcelona City Primary Care. Catalan Health Institute. ParticipantsAll women attended by primary care teams who in January 2014 had received bisphosphonate treatment for at least five years were included and followed for another five years. InterventionPatients were classified according to their risk of new fractures, defined as those who had a history of osteoporotic fracture and/or who received treatment with an aromatase inhibitor, and the continuity or deprescription of the bisphosphonate treatment was analyzed over fiver year follow-up. Main measurementsThe cumulative incidence of fractures and the incidence density were calculated and analyzed using logistic regression and Cox models. ResultsWe included 3680 women. There were no significant differences in fracture risk in high-risk women who discontinued versus continued bisphosphonate treatment (hazard ratio [HR] 1.17, 95% confidence interval [CI] 0.87–1.58 for total osteoporotic fractures). However, discontinuers at low risk had a lower incidence of fracture than continuers. This difference was significant for vertebral fractures (HR 0.64, 95% CI 0.47–0.88) and total fractures (HR 0.77, 95% CI 0.64–0.92). ConclusionOur results suggest that deprescribing bisphosphonates in women who have already received five years of treatment does not increase fracture risk. In low-risk women, continuing this treatment might could even favor the appearance of new osteoporotic fractures.

Skeletal outcomes of patients with osteogenesis imperfecta during drug holiday of bisphosphonates: a real-world study

PurposeThis study aimed to investigate the skeletal outcomes of patients with osteogenesis imperfecta (OI) who received bisphosphonate (BP) treatment and entered drug holiday after achieving an age- and sex-specific bone mineral density (BMD) reference.MethodsPatients with OI receiving BP treatment were enrolled when they entered drug holidays of BPs. The skeletal outcomes were evaluated in detail during the drug holiday, including BMD, X-ray of the bone, bone fracture incidence, and bone turnover biomarkers. The pathogenic mutations of OI were identified by next-generation sequencing and confirmed by Sanger sequencing.ResultsA total of 149 OI patients (127 juveniles and 22 adults) who entered drug holidays after nearly 4 years of BP treatment were included. Areal BMD at the lumbar spine increased from 0.934 ± 0.151 to 0.990 ± 0.142 g/cm2 and was stable in the second (1.029 ± 0.176 g/cm2) and third years (1.023 ± 0.174 g/cm2) of BP drug holidays, and BMD at the femoral neck, trochanter, and total hip had no significant change, but it was gradually inferior to that of the same-gender juveniles in the second and third years of the drug holiday. BMD at the lumbar spine and proximal hip did not change and was inferior to that of the same-gender adults. The average time of fractures fluctuated from 0.18 to 0.08 per year in juveniles, while only one adult suffered from a fracture during BP drug holidays. Bone turnover markers were in the normal range, except for a mildly high level of β-carboxy-terminal cross-linked telopeptide of type 1 collagen in the juvenile group. A total of 17 (11.4%) patients received BP retreatment because of bone loss during the drug holiday. OI type III and type IV and COL1A2 mutation were correlated to a longer duration of BP treatment to enter drug holidays (all p < 0.05). Old age at initial treatment (OR, 1.056) and OI type III (OR, 10.880) were correlated to a higher risk of BP retreatment.ConclusionsOI patients will undergo nearly 4 years of BP treatment to achieve drug holidays. During the 3 years of the drug holiday, the patients’ BMD is stable, and fracture incidence does not increase significantly. Patients are more inclined to need retreatment during drug holidays owing to the late start of BP treatment and more severe OI phenotypes.

Clinical and radiological outcomes of denosumab and teriparatide treatment in elderly patients with osteoporotic spinal compression fracture without vertebroplasty

Objective Vertebroplasty is a common treatment for osteoporotic spinal compression fractures, but it poses complication risk. Therefore, we investigated the clinical and radiological outcomes of conservative treatment using a combination of denosumab and teriparatide. Methods This study included 86 patients aged 75 or older who were diagnosed with osteoporotic spinal compression fracture from January 2011 to April 2021. The patients were then categorized into those who received denosumab and teriparatide combination treatment without vertebroplasty(group A) and those who received bisphosphonate treatment and underwent vertebroplasty (group B). Several parameters were analyzed: age, sex, underlying diseases, BMI, hospital stay, the time of ambulation start, BMD, VAS score, compression ratio, regional Cobb angle, and local kyphotic angle. Results As compared to group A, group B showed a relatively shorter hospital stay and time until starting ambulation, but without statistical significance. The VAS scores measured at the time of injury, post-treatment, 3months post-injury, and 1year post-injury did not show statistically significant differences between the groups. In contrast, the mean BMD measured at the time of injury and 1year post-injury demonstrated statistically significant improvements in group A compared to group B. The differences in the compression ratio, regional Cobb angle, and local kyphotic angle measured at the time of injury and 1year post-injury were not statistically significant. Conclusion Combination treatment without vertebroplasty did not show significant differences in either clinical or radiologic results compared to vertebroplasty cases. Therefore, denosumab and teriparatide combination treatment could be considered as an alternative option for osteoporotic spinal compression fracture patients. Keywords: Osteoporosis; Vertebral compression fracture; Vertebroplasty; Elderly patients; Bone density

Clinical features, treatments and outcomes of calcinosis in adult patients with dermatomyositis: a single cohort study.

The occurrence of calcinosis cutis as a clinical feature of dermatomyositis in adult patients is not well understood. Cohort studies of adult patients with calcinosis are rare. We systematically describe the clinical features, treatments and outcomes of adult patients with calcinosis. We initially enrolled 627 adult DM patients. Of those enrolled, 35 (5.6%) were found to have calcinosis. We analysed the clinical features associated with calcinosis in this subgroup. The risk factors associated with calcinosis were analysed using the Poisson regression model. Multivariate analysis showed that a younger age at disease onset [odds ratio (OR) = 0.945, 95% CI 0.925, 0.966, P < 0.001], dysphagia (OR = 2.609, 95% CI 1.189, 5.728, P = 0.017), skin ulcer (OR = 5.705, 95% CI 3.041, 10.705, P < 0.001) and the presence of anti-nuclear matrix protein 2 antibody (OR = 5.917, 95% CI 2.754, 12.714, P < 0.001) were independently associated with calcinosis. In both the low- and high-dose prednisone treatment groups, no difference in treatment response was seen between the bisphosphonate treatment group and the group not receiving bisphosphonate treatment (P = 1.000 and P = 0.375, respectively). A follow-up study revealed that the mortality rate of the calcinosis group was 5.7%. Additionally, 60.6% of the cases had a chronic polycyclic disease course and 17.1% had mild complications secondary to calcinosis. Calcinosis is an uncommon, but significant clinical feature in adult patients with DM. Bisphosphonates were not found to effectively treat calcinosis, however, the overall health outcomes of adult DM patients with calcinosis were favourable.

Surgical management of Gorham-Stout syndrome involving the cervical spine with bilateral pleural effusion: A case report and literature review.

Gorham-Stout syndrome (GSS) is a rare disease characterized by spontaneous and progressive osteolysis caused by benign proliferation of lymphatic vessels or capillaries. It most commonly occurs in children or young individuals without any inherited predisposition. GSS most commonly affects the shoulder girdle, pelvis, ribs and skull. Its diagnosis is mainly based on radiological and pathological findings. The present study reports on the case of a 22-year-old male patient diagnosed with GSS involving the C1-T1 vertebrae accompanied by bilateral pleural effusion. Resection of the occipital and cervical vertebral lesions and spinal reconstruction using an internal fixator were successfully performed via the posterior approach. After the surgery, the patient received bisphosphonate treatment and vitamin D supplementation. The pleural effusion gradually decreased. At the 18-month follow-up visit, no evidence of new bone obstruction was present and the patient had no neurological sequelae.

Femur Fracture Caused by Falling of a Boy with Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is the most common hereditable cause of bone fragility in children. A Japanese 2-year-old boy fell accidentally from a slide, sustaining a femur shaft fracture. Several maternal family members had experienced episodes of hearing impairment and bone fracture. The injury mechanism was clear and competent. Child abuse was unlikely. Strong family history and presence of blue sclera confirmed the OI diagnosis. Any doctor treating pediatric femur fractures should recall the rare cause of OI. Clinical evaluation alone without a family interview might not complete the diagnosis with OI. We continued proposing to his parents the benefit of receiving bisphosphonate treatment.

Osteoporosis-pseudoglioma syndrome: clinical, genetic, and treatment-response study of 10 new cases in Greece.

Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal-recessive disorder, characterized by severe osteoporosis and early-onset blindness. Loss of function mutations in the gene encoding low-density lipoprotein receptor-related protein 5 (LRP5) have been established as the genetic defect of the disease. We report the clinical and genetic evaluation of ten OPPG cases in eight related nuclear families and their close relatives. Bone mineral density (BMD) in OPPG patients was assessed by dual-energy X-ray absorptiometry (DXA). Genotyping of LRP5 gene and targeted detection of index mutation were performed by DNA direct sequencing. Four patients were introduced to bisphosphonates. Mutational screening of LRP5 gene revealed the c.2409_2503+79del deletion in homozygous state, expected to result in a truncated protein. Among 44 members of the pedigree, 10 (22%) were identified homozygous and 34 (59%) heterozygous for this mutation. All patients had congenital blindness and7 of them had also impaired bone mineral density. Four of them received bisphosphonates and responded with decreased bone pain and improvement in BMD; however, 3 patients presented with one fracture during treatment.Conclusion: The current study presents the molecular and clinical profiles of 10 new OPPG cases, being part of an extended pedigree. Patients who received bisphosphonate treatment responded well with increase in their BMD, though fractures occurred during therapy. What is known: • OPPG syndrome is a rare genetic disorder characterized by congenital blindness and juvenile osteoporosis. • Loss of function mutations in the gene encoding low-density lipoprotein receptor-related protein 5 (LRP5) is the genetic defect of the disease. What is new: • Genetic and clinical phenotype of 10 new OPPG patients. • The ten new OPPG patients presented with phenotypical variability in osseous manifestations.

Bone mineral density in osteoporotic patients with pyogenic vertebral osteomyelitis: effect of early versus late treatment for osteoporosis.

Due to absence of concern and proper guidelines, management of bone loss or osteoporosis in PVO is often neglected or delayed. A retrospective cohort study was planned to investigate differences in bone mineral density (BMD) in PVO patients with osteoporosis according to the timing of osteoporosis treatment. The PVO cohort consisted of 192 patients with osteoporosis who visited our institution between January 2003 and March 2015 and received bisphosphonate treatment for osteoporosis. According to the interval between PVO diagnosis and initiation of bisphosphonate, the patients were divided into three groups: group A (within 6weeks after PVO diagnosis), group B (between 6weeks and 3months after diagnosis), and group C (more than 3months after PVO diagnosis). The percent increase in total femoral BMD in group A was significantly larger than that in group B at 2-year follow-up (p = 0.036). Similarly, the percent increase in trochanteric (p = 0.008) and total femoral (p = 0009) BMD in group A was significantly larger than that in group C at 2-year follow-up. Even after multivariate adjustment, total femoral BMD changes were significantly associated with the treatment group. Group B (odds ratio = 2.824, p = 0.013) and group C (odds ratio = 3.591, p = 0.001) were more significantly associated with total femoral BMD decreases at 2-year follow-up compared with group A. Early bisphosphonate treatment within 6weeks after PVO diagnosis (group A) was significantly associated with superior outcome in femoral BMD at 2-year follow-up, compared to that with late treatment (groups B and C).

Long-term follow-up in osteogenesis imperfecta type VI.

Osteogenesis imperfecta (OI) type VI is an ultra-rare bone fragility disorder caused by recessive mutations in SERPINF1. Here, we describe long-term outcomes in OI type VI and compare the clinical phenotypes caused by different types of SERPINF1 mutations. This study includes a retrospective chart review of 13 individuals with OI type VI. In the absence of therapy, lumbar spine areal bone mineral density (BMD) did not increase during childhood and longitudinal growth seemed to stall after the age of 6 to 8years. The phenotype was similar between individuals with different types of SERPINF1 mutations. Intravenous bisphosphonate treatment was associated with an increase in lumbar spine areal BMD and some reshaping of compressed vertebral bodies. Patients who had started bisphosphonate treatment early (before the age of 6years) were taller than patients who had received bisphosphonate treatment later during their growing years. Lower extremity fractures were frequent despite bisphosphonate treatment and scoliosis was present in all patients who had reached the final height. Most patients had restricted mobility. In four patients, intravenous bisphosphonate treatment was eventually substituted by subcutaneous injections of denosumab, without clear changes in the clinical picture. Patients with OI type VI who received intravenous bisphosphonate treatment during growth had an increase in lumbar spine areal BMD, a higher final height z-score, and presented some reshaping of vertebral bodies. More effective treatment modalities are clearly required in OI type VI.

Effect of bisphosphonate initiation at week 2 versus week 12 on short-term functional recovery after femoral neck fracture: a randomized controlled trial

SummaryThe appropriate time to initiate bisphosphonate treatment after a fragility fracture has not yet been established. In this study, we found no significant differences in short-term functional recovery between femoral neck fracture patients who received bisphosphonate treatment at 2 versus 12 weeks after hemiarthroplasty.IntroductionBisphosphonate is the mainstay therapy for prevention and treatment of osteoporosis. The aim of this study was to investigate the effect of bisphosphonate initiation on short-term functional recovery in femoral neck fracture patients at 2 versus 12 weeks after hemiarthroplasty.MethodsOne hundred patients were randomly allocated into two groups in a parallel group designed, randomized, controlled trial. Both groups received risedronate 35 mg/week at either 2 or 12 weeks after hemiarthroplasty. All patients received calcium and vitamin D supplementation. Functional recovery was assessed by de Morton Mobility Index, Barthel Index, EuroQol 5D, visual analog scale, 2-min walk test, and timed get-up-and-go test at 2 weeks, 3 months, and 1 year after surgery.ResultsAt the 3-month follow-up, all functional outcome measures showed significant improvement in both groups. There were no statistically significant differences in any of the functional outcomes between groups at both the 3-month and 1-year follow-ups. Although patients who received bisphosphonate initiation at week 2 had lower serum calcium level at 3 months and more overall adverse events than patients in the week 12 group, no patients in either group discontinued their prescribed medications.ConclusionsWhile underpowered, the findings of this study suggest that there were no significant differences in short-term functional recovery or significant adverse events between the two bisphosphonate groups. Thus, the initiation of bisphosphonate therapy may be considered as early as 2 weeks after femoral neck fracture. It is important that low serum calcium and vitamin D status must be corrected with calcium and vitamin D supplementation prior to or at the time of bisphosphonate initiation.Clinical trial registration numberThis study was registered in the database via the Protocol Registration and Results System (PRS) (NCT02148848).

Computed tomographic assessment of early changes of the mandible in bisphosphonate-treated patients

To compare the computed tomography (CT) features of mandibular cancellous and cortical bones between patients with bisphosphonate (BP) administration and those without and to assess the early changes of the mandible in BP-treated patients. Twenty-four BP-treated patients suffering from medication-related osteonecrosis of the jaw (MRONJ) were enrolled in this study. For comparison, 20 patients suffering from osteomyelitis and 20 patients without pathology in the jaw were also enrolled, all of whom did not receive BP treatment. The CT values of the cancellous and cortical bone and the cortical bone widths were measured. In the MRONJ and osteomyelitis groups, there were significant differences in the CT values of cancellous and cortical bones between the affected and unaffected areas. In patients with stage 0 MRONJ, a significant difference was noted in the cancellous bone CT values between these areas. The cancellous bone CT values at the affected and unaffected areas in the BP-treated group were significantly higher than in the control groups. In patients with stage 0 MRONJ, the cancellous bone CT values at the affected area were also significantly higher than in the healthy patients. The cortical bone widths in the unaffected areas in the BP-treated patients were significantly larger than in healthy patients. The cancellous bone CT values were higher in the BP-treated group, including in patients with stage 0 MRONJ, and CT may provide useful quantitative information.

Osteotomy Healing in Children With Osteogenesis Imperfecta Receiving Bisphosphonate Treatment

A decade ago our group had reported that osteotomy healing was commonly delayed in children with moderate to severe osteogenesis imperfecta (OI) who were treated with intravenous pamidronate infusions. We subsequently maintained a bisphosphonate infusion-free interval of 4 months after osteotomy and changed the surgical approach (use of an osteotome instead of a power saw). In addition, zoledronic acid has become the standard intravenous bisphosphonate for treatment of OI at our institution. In the present study, we compared osteotomy healing before and after these changes were instituted. We evaluated bone healing post-osteotomy on standard radiographs after 261 intramedullary rodding procedures involving osteotomies (139 femur, 112 tibia) in 110 patients (age at surgery 1.2 to 20.4 years). Delayed healing was diagnosed when the osteotomy line was visible 12 months after the event. We observed delayed bone healing after 48 of the 114 osteotomies (42%) performed with the new approach, and in 106 of the 147 osteotomies (72%) using the previous approach (p = 0.001). The odds for delayed osteotomy healing were significantly lower with the new approach even after adjustment for age, sex, height Z-score, weight Z-score, OI type, and bone involved (odds ratio = 0.17; 95% confidence interval 0.16-0.47). Thus, delayed osteotomy healing occurred less frequently in the past 10 years than in the decade before that. It is likely that this improved result is attributable to the implemented changes in both medical and surgical management.

What is the impact of bisphosphonate therapy upon dental implant survival? A systematic review and meta-analysis.

A systematic review and meta-analysis are carried out to assess the scientific evidence that bisphosphonate therapy can decrease the success rate of dental implants. The PubMed (Medline) database was used to search for articles published up until February 22, 2014. The meta-analysis was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). The Newcastle-Ottawa scale (NOS) was used to assess study quality. The combinations of search terms resulted in a list of 256 titles. Fourteen finally met the inclusion criteria and were thus selected for inclusion in the systematic review. Eight studies (six retrospective and two prospective) were included in the meta-analysis, with a total of 1288 patients (386 cases and 902 controls) and 4562 dental implants (1090 dental implants in cases and 3472 in controls). The summary odds ratio (OR=1.43, P=0.156) indicates that there is not enough evidence that bisphosphonates have a negative impact upon implant survival. According to the number need to harm (NNH), over 500 dental implants are required in patients receiving bisphosphonate treatment to produce a single implant failure. Our results show that dental implant placement in patients receiving bisphosphonates does not reduce the dental implant success rate. On the other hand, such patients are not without complications, and risk evaluation therefore must be established on an individualized basis, as one of the most serious though infrequent complications of bisphosphonate therapy is bisphosphonate-related osteonecrosis of the jaws. Given the few studies included in our meta-analysis, further prospective studies involving larger sample sizes and longer durations of follow-up are required to confirm the results obtained.

Assessment of Bone Microarchitecture in Postmenopausal Women on Long-Term Bisphosphonate Therapy With Atypical Fractures of the Femur

Reports of atypical femoral fractures (AFFs) in patients receiving long- term bisphosphonate therapy have raised concerns regarding the genesis of this rare event. Using high-resolution peripheral quantitative computed tomography (HR-pQCT), we conducted a study to evaluate bone microarchitecture in patients who had suffered an AFF during long-term bisphosphonate treatment. The aim of our study was to evaluate if bone microarchitecture assessment could help explain the pathophysiology of these fractures. We compared bone volumetric density and microarchitectural parameters measured by HR-pQCT in the radius and tibia in 20 patients with AFFs with 35 postmenopausal women who had also received long-term bisphosphonate treatment but had not experienced AFFs, and with 54 treatment-naive postmenopausal women. Control groups were similar in age, body mass index (BMI), and bone mineral density (BMD). Mean age of the 20 patients with AFFs was 71 years, mean lumbar spine T-score was -2.2, and mean femoral neck T-score was -2. Mean time on bisphosphonate treatment was 10.9 years (range, 5-20 years). None of the patients had other conditions associated with AFFs such as rheumatoid arthritis, diabetes or glucocorticoid use. There were no statistically significant differences in any of the parameters measured by HR-pQCT between postmenopausal women with or without treatment history and with or without history of atypical fractures. We could not find any distinctive microarchitecture features in the peripheral skeleton of women who had suffered an atypical fracture of the femur while receiving bisphosphonate treatment. This suggests that risk of developing an atypical fracture is not related to bone microarchitecture deterioration. Our results indicate that there may be other individual factors predisposing to atypical fractures in patients treated with bisphosphonates, and that those are independent of bone microarchitecture. In the future, identification of those factors could help prevent and understand the complex physiopathology of these rare events.

Bisphosphonates for Osteoporosis in Nonmetastatic Prostate Cancer Patients Receiving Androgen-deprivation Therapy: A Systematic Review and Meta-analysis

This systematic review was conducted to assess the efficacy and safety of bisphosphonates for prevention and treatment of osteopenia or osteoporosis in men with non-metastatic prostate cancer receiving androgen- deprivation therapy. We searched for randomised controlled trials (RCTs) of bisphosphonates compared with placebo from Pubmed, Embase, the Cochrane Library, and ISI - Science Citation Index. Meta-analyses of pre- specified outcomes (bone mineral density, fractures, and adverse events) were performed using Review Manager. Ten RCTs with a total patient population of 1,017 were identified. There was generally more improvement in bone mineral density of the lumbar spine for patients who received bisphosphonate treatment than placebo or other medical treatment at 12 months (WMD 6.02,95%CI 5.39 to 6.65). Similar effects were also observed for total hip, trochanter or femoral neck bone mineral density. However, there was no significant reduction in fractures. Fever and gastrointestinal symptoms were the most common adverse events (10.4% vs. 1.2%; 0.10% vs. 0.03%). Currently, our meta-analysis suggested that oral and intravenous bisphosphonates caused a rapid increase in spine and hip or femoral BMD in non-metastatic prostate cancer patients receiving androgen-deprivation therapy. Fever and gastrointestinal symptoms were common with the use of bisphosphonates. These short-term trials (maximum of 12 months) did not show fracture reduction. In future, more efficient performance of higher quality, more rigorous, large sample, long-term randomised controlled trials (>12 months) are needed where outcomes are detailed.