Bisphosphonate Treatment Research Articles

Using DEXA to diagnose impending atypical femoral fracture in an asymptomatic patient on long term bisphosphonates: A case report of a missed opportunity for fracture prevention.

We report a patient who sustained an AFF (Atypical femoral fractures) after 15 years of bisphosphonate treatment. DEXA scans can be utilized to identify early evidence of AFF in asymptomatic patients up to 9 years before the development of an AFF.

7635 Severe Osteoporosis in a Patient with Heterotopic Calcification: A Case Report

Abstract Disclosure: D. Salih Bacha: None. L.Z. Khan: None. Background: While osteoporosis and heterotopic ossification (HO) are distinct conditions affecting bone health, their coexistence poses intriguing clinical challenges. Osteoporosis, characterized by increased bone fragility, typically results from various factors such as aging, steroid use, or malabsorption. HO is a condition where bone forms abnormally in soft tissues. Risk factors that predispose to HO include male sex, spinal cord injury, trauma, surgery, and genetic factors. Treatment of HO is typically surgical resection and NSAIDs. Initial evidence supported the use of bisphosphonates for preventing ectopic bone formation post-trauma, but recent data failed to show significant benefit in HO prevention. This case presents a patient with unique challenges of both HO and bone fragility with multiple severe vertebral fractures. Case: A 44-year-old male patient had a major motor vehicle accident necessitating multiple recurrent abdominal surgeries. During one exploratory laparotomy, diffuse mesenteric calcifications were noted, indicative of HO. A baseline Dual X-ray Absorptiometry (DXA) scan revealed bone density of 1.003 g/cm2 and 0.788 g/cm2 at the spine and femoral neck, respectively, concerning for osteopenia. He was started on zoledronic acid in preparation for upcoming intestinal transplant. Few months after the transplant, he was started on daily tacrolimus and hydrocortisone for immunosuppression. Within months, he experienced sudden back pain while riding an elevator, and was found to have acute fractures in T8 and T9 vertebrae. A repeat DXA scan showed a further decline in bone density to 0.909 g/cm2 and 0.748 g/cm2 at the spine and femoral neck, respectively. Within a year, additional fractures occurred in the thoracic and lumbar spine (T10, T11, T12, L1, L2, L3, and L4), requiring multiple kyphoplasty interventions. Over time, worsening kyphosis, back pain, and height loss occurred, significantly affecting the patient's quality of life. He continued receiving yearly zoledronic acid infusions and underwent regular DXA scans, which revealed mild improvement in his bone density. Currently, there are no established guidelines specifying the optimal duration for bisphosphonate treatment in such cases. Therefore, our individualized treatment plan involves a tentative 10-year course of bisphosphonate treatment with yearly assessment of bone mineral density. Conclusion: Although the patient had some risk factors for osteoporosis, including daily steroid and tacrolimus use, the severity and frequency of his fractures suggested a potential synergy between osteoporosis and HO, where the formation of heterotopic calcifications may have been exacerbating his bone loss. The coexistence of osteoporosis and HO in this patient underscores the need for individualized care and establishment of treatment guidelines in patients with multiple bone disorders. Presentation: 6/3/2024

7077 A Rare Case Of Hypophosphatasia Presenting With Osteoporosis In A Young Female Patient- Diagnostic Delay In Hypophosphatasia

Abstract Disclosure: R. Abdelmasih: None. I. Ali: None. Introduction: Hypophosphatasia is a rare hereditary cause of secondary osteoporosis that affects 1/100.000 individuals. The rate of osteoporosis due to hypophosphatasia is probably underestimated as it likely goes undiagnosed in heterogeneous or milder cases. We present a case of Hypophosphatasia that presented initially with osteoporosis and went misdiagnosed for years with intermittent treatment of Bisphosphonate, luckily with no atypical fractures that prompted different course of management for osteoporosis. Case Presentation: A 44-year-old female with a history of rheumatoid arthritis and osteoporosis diagnosed 7 years prior and treated with intermittent bisphosphonate which was discontinued due to side effects including muscle aches and bone pains, presented to our endocrinology clinic to establish care for osteoporosis. Patient denied prior fractures. She reported jaw pain that is being evaluated by otolaryngology and a dentist. Family history is negative. DEXA scan showed Z scores of -1.1, -1.8, and -2.2 of the lumbar spine, femoral neck, and total femur respectively. Laboratory workup showed consistently low alkaline phosphatase (ALP) 25, 20, <20 U/L (ref range 34-123), elevated Vitamin B6 of 167 nmol/L (ref range 20-125), normal parathormone, calcium, phosphate, Vit D, magnesium, and liver enzymes. Genetic testing was sent for Tissue non-specific alkaline phosphatase (TNALP). Hypophosphatasia was diagnosed based on clinical and laboratory findings, patient was started on Asfotase alfa. Clinical course is to be followed. Discussion: Hypophosphatasia is a rare hereditary disorder due to mutation of (TNALP). In normal induvial, TNALP breaks down pyrophosphate to phosphate. It also plays a role in transferring Vit B6 into the tissues. Hence, clinical presentation due to impaired calcium-phosphate hemostasis is broad including musculoskeletal pain, pseudofractues, dental abscess, and neurological symptoms (due to accumulation of Vit B6). The clinical picture varies depending on the heterogenicity of ALPL mutation. Genetic testing is not mandated to establish diagnosis, clinical presentation and laboratory testing including low ALP and elevated Vit B6 are sufficient. However, genetic testing and counseling are recommended for the patient’s sake and their family members. Antiresorptive bone therapy is contraindicated due to a further decrease of bone turnover with reported cases of increased risk of atypical femur fracture, Bone density is reported to improve with enzyme replacement therapy with bone-targeting recombinant alkaline phosphatase (Asfotase Alpha), if further treatment is needed, anabolic treatment is preferred. We present this case to shed light on such a rare disease to decrease rates of underdiagnosis or delayed diagnosis in young patients presenting with osteoporosis for prompt treatment and improved quality of life of these patients. Presentation: 6/2/2024

Efficacy and safety of teriparatide vs. bisphosphonates and denosumab vs. bisphosphonates in osteoporosis not previously treated with bisphosphonates: a systematic review and meta-analysis of randomized controlled trials

SummaryThe study found that in osteoporosis patients who had not previously received bisphosphonate treatment and were in a treatment cycle of over 12 months, both teriparatide and denosumab significantly increased bone mineral density compared to bisphosphonates. Additionally, teriparatide was also shown to significantly decrease the risk of fractures.ObjectiveThe systematic review and meta-analysis aimed to assess and compare the safety and efficacy of teriparatide vs. bisphosphonates and denosumab vs. bisphosphonates in patients with osteoporosis who had not previously received bisphosphonates.MethodsWe conducted a search of published literature from inception to May 31, 2023, including databases such as PubMed, Embase, Cochrane Library, CNKI, SinoMed, VIP, and WanFang. The study only included head-to-head randomized controlled trials (RCTs) that compared teriparatide and denosumab with bisphosphonates to treat patients with osteoporosis. Fixed-effect model and random-effect model were used due to clinical heterogeneity. Meta-analysis was performed via Stata 17.0.ResultsA total of 6680 patients were enrolled across 23 eligible trials. The results of the meta-analysis showed that teriparatide was superior to bisphosphonates in decreasing the risk of fracture (risk ratio (RR) = 0.61, 95% confidence interval (CI) (0.51, 0.74), P < 0.001). Denosumab showed no benefit compared to bisphosphonates in reducing the risk of fracture in treating osteoporosis (RR 0.99, 95% CI (0.62, 1.57), P = 0.96). Compared with bisphosphonates, teriparatide and denosumab could significantly improve femoral neck, total hip, and lumbar spine bone mineral density (BMD) (P < 0.05). Furthermore, teriparatide and denosumab did not increase the incidence of adverse events (teriparatide vs. bisphosphonates, RR 0.92, 95% CI (0.79, 1.08), P = 0.32; denosumab vs. bisphosphonates, RR 0.98, 95% CI (0.95, 1.02), P = 0.37).ConclusionsTeriparatide is superior to bisphosphonates in decreasing the risk of fracture in patients with osteoporosis. In addition, teriparatide and denosumab were more efficacious than bisphosphonates in increasing the percentage change in BMD at the femoral neck, total hip, and lumbar spine.

Bisphosphonates and Antibiotics Combination Therapy for Chronic Low Back Pain Associated with Modic Change: A Quasi-Experimental Study

Background: Although effective treatments are still lacking for chronic low back pain (CLBP) associated with Modic changes (MC), in recent years, the efficacy of bisphosphonate and antibiotic treatment has been tested separately with variable success. This study aimed to compare the effectiveness of combined therapy of bisphosphonate and antibiotics versus single-drug therapy in CLBP patients with MC.Methods: This quasi-experimental study was carried out from October 2019 to September 2020 according to 1964 Helsinki declaration among 60 adult CLBP patients with MC (confirmed by magnetic resonant imaging) and randomly allocated in Group-A (n=20): Zoledronic acid (ZA) only, Group-B (n=20): amoxicillin-clavulanate only, and Group-C (n=20): both ZA and amoxicillin-clavulanate. The primary outcomes were measured by the visual analog scale (VAS) and Roland Morris disability questionnaire (RMDQ) at follow-ups after 1 month, 100 days, and 6 months. Per-protocol analysis was performed using SPSS 24.Results: Out of the 60 patients, 43 patients (72%) completed all three follow-ups. The VAS score gradually decreased in all groups after treatment, wherein Group-C patients had the significantly lowest score at the 2nd and 3rd follow-ups (2.87±0.80 and 1.68±0.70, respectively) compared to Group-A (3.40±0.63 and 2.20±0.67, respectively) and Group-B (3.50±0.52 and 2.41±0.66,respectively). In addition, RMDQ also decreased significantly after 1 month compared to pretreatment (p&lt;0.05) in all 3 groups, and this gradual decrement was continued until 6 months of treatment. However, it was reduced more in Group-C (6.26±0.70) than in group-A (6.69±1.40) and Group-B (7.75±1.21) at the end of the 3rd follow-up. Moreover, Group-C patients had the highest satisfaction level and lowest number of days with absence from work score compared to A and B (p&lt;0.05). However, adverse effects were relatively higher in Group-C than A and B (p&gt;0.05).Conclusion: Bisphosphonates and antibiotics combination therapy is more effective than single-drug therapy for CLBP associated with MC.

Impact of bisphosphonate treatment on bone mineral density after kidney transplant.

Mineral bone disease is associated with chronic kidney disease and persists after kidney transplantation. Immunosuppressive treatment contributes to the pathogenesis of this disease. Bisphosphonate treatments have shown positive but indefinite results. To evaluate the effectiveness and safety of bisphosphonate treatment on post kidney transplantation bone mineral density (BMD). We included kidney transplant recipients (KTRs) whose BMD was measured after the operation but before the initiation of treatment and their BMD was measured at least one year later. We also evaluated the BMD of KTRs using two valid measurements after transplantation who received no treatment (control group). Out of 254 KTRs, 62 (39 men) were included in the study. Bisphosphonates were initiated in 35 KTRs in total (20 men), 1.1 ± 2.4 years after operation and for a period of 3.9 ± 2.3 years while 27 (19 men) received no treatment. BMD improved significantly in KTRs who received bisphosphonate treatments (from -2.29 ± 1.07 to -1.66 ± 1.09, P < 0.0001). The control group showed a non-significant decrease in BMD after 4.2 ± 1.4 years of follow-up after surgery. Kidney function was not affected by bisphosphonate treatment. In KTRs with established osteoporosis, active treatment had a similar and significant effect on those with osteopenia or normal bone mass. In this retrospective study of KTRs receiving bisphosphonate treatment, we showed that active treatment is effective in preventing bone loss irrespective of baseline BMD.

Outcome of tooth extraction in patients receiving bisphosphonate treatment – surgical protocol and risk factors

Outcome of tooth extraction in patients receiving bisphosphonate treatment – surgical protocol and risk factors

The Potential of Enamel Matrix Derivative in Countering Bisphosphonate-Induced Effects in Osteoblasts.

The suppressive effect of bisphosphonates (BPs) on bone metabolism is considered to be a major cause of medication-related osteonecrosis of the jaw (MRONJ). Enamel matrix derivative (EMD) stimulates and activates growth factors, leading to the regeneration of periodontal tissues. In this study, we aimed to explore the potential of EMD in reversing the detrimental effects of BPs on human fetal osteoblasts (hFOBs) and osteosarcoma-derived immature osteoblasts (MG63s) by assessing cell viability, apoptosis, migration, gene expression, and protein synthesis. While the suppressive effect of zoledronate (Zol) on cell viability and migration was observed, the addition of EMD significantly mitigated this effect and enhanced cell viability and migration. Furthermore, an increased apoptosis rate induced by Zol was decreased with the addition of EMD. The decreased gene expression of alkaline phosphatase (ALP), osteocalcin (OC), and the receptor activator of nuclear factors kappa-B ligand (RANKL) caused by BP treatment was reversed by the co-addition of EMD to hFOB cells. This trend was also observed for ALP and bone sialoprotein (BSP) levels in MG63 cells. Furthermore, suppressed protein levels of OC, macrophage colony-stimulating factor (M-CSF), BSP, and type 1 collagen (COL1) were recovered following the addition of EMD. This finding suggests that EMD could mitigate the effects of BPs, resulting in the recovery of cell survival, migration, and gene and protein expression. However, the behavior of the osteoblasts was not fully restored, and further studies are necessary to confirm their effects at the cellular level and to assess their clinical usefulness in vivo for the prevention and treatment of MRONJ.

Major aspects of the use of bisphosphonates and the formation of osteonecrosis in the involvement of dental implants: a systematic review

Introduction: Bisphosphonates are widely used to treat osteoporosis and malignant tumors due to their effectiveness in increasing bone density and inhibiting bone resorption. Dental patients receiving bisphosphonate treatment are at higher risk of bisphosphonate-related osteonecrosis of the jaws (BRONJ), necessitating dentists' awareness of these risks. Objective: It was to highlight the main aspects of the use of bisphosphonates and the formation of osteonecrosis in the involvement of dental implants, as well as possible treatments. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from April to July 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 120 articles were found, 40 articles were evaluated in full and 15 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 14 studies with a high risk of bias and 21 studies that did not meet GRADE and AMSTAR-2. Most studies did not show homogeneity in their results, with X2=89.5%&gt;50%. Therefore, the present study suggests that patients undergoing treatment with BFs should be informed about the potential risk of BRONJ. Furthermore, it would be advisable for providers responsible for BF therapy to refer patients for dental check-ups before starting treatment, allowing for patient monitoring by a multidisciplinary team. Although the morbidity rate of this pathology is not high, prevention should be mandatory, thus avoiding mutilating and painful processes. However, if surgery is necessary, the use of these new adjuvant therapies, such as lowlevel laser therapy and magnetotherapy, can be proposed in the treatment of BRONJ. It is essential to increase our caseload and also involve other institutions in the use of these new effective and safe therapies in BRONJ.

Can Bisphosphonate Therapy Reduce Overall Mortality in Patients With Osteoporosis? A Meta-analysis of Randomized Controlled Trials.

For patients with osteoporosis, bisphosphonate therapy can reduce the risk of fractures, but its effect on reducing mortality remains unclear. Previous studies on this topic have produced conflicting results and generally have been too small to definitively answer the question of whether bisphosphonate therapy reduces mortality. Therefore, a meta-analysis may help us arrive at a more conclusive answer. In a large meta-analysis of placebo-controlled randomized controlled trials (RCTs), we asked: (1) Does bisphosphonate use reduce mortality? (2) Is there a subgroup effect based on whether different bisphosphonate drugs were used (zoledronate, alendronate, risedronate, and ibandronate), different geographic regions where the study took place (Europe, the Americas, and Asia), whether the study was limited to postmenopausal female patients, or whether the trials lasted 3 years or longer? We conducted a systematic review using multiple databases, including Embase, Web of Science, Medline (via PubMed), Cochrane Library, and ClinicalTrials.gov, with each database searched up to November 20, 2023 (which also was the date of our last search), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included randomized, placebo-controlled clinical trials with participants diagnosed with osteoporosis and receiving bisphosphonate treatment. We excluded papers posted to preprint servers, other unpublished work, conference abstracts, and papers that were registered on ClinicalTrials.gov but were not yet published. We collected 2263 records. After excluding records due to study type, study content not meeting the inclusion criteria, and duplicates, our meta-analysis included 47 placebo-controlled RCTs involving 59,437 participants. Data extraction, quality assessment, and statistical analyses were performed. The evaluation of randomized trials for potential bias was conducted using the revised Cochrane Risk of Bias tool. This assessment encompassed factors such as sequence generation, allocation concealment, subject blinding, outcome assessor blinding, incomplete outcome data, and reporting bias. Some studies did not provide explicit details regarding random sequence generation, leading to a high risk of selection bias. A few studies, due to their open-label nature, were unable to achieve double-blind conditions for both the subjects and the researchers, resulting in intermediate performance bias. Nevertheless, the overall study quality was high. Due to the low heterogeneity among the studies, as evidenced by the low statistical heterogeneity (that is, a low I2 statistic), we opted for a fixed-effects model, indicating that the effect size is consistent across the studies. In such cases, the fixed-effects model can provide more precise estimates. According to the results of the funnel plot, we did not find evidence of publication bias. The use of bisphosphonates did not reduce the overall risk of mortality in patients with osteoporosis (risk ratio 0.95 [95% CI 0.88 to 1.03]). Subgroup analyses involving different bisphosphonate drugs (zoledronate, alendronate, risedronate, and ibandronate), regions (Europe, the Americas, and Asia), diverse populations (postmenopausal female patients and other patients), and trials lasting 3 years or longer revealed no associations with reduced overall mortality. Based on our comprehensive meta-analysis, there is high-quality evidence suggesting that bisphosphonate therapy for patients with osteoporosis does not reduce the overall risk of mortality despite its effectiveness in reducing the risk of fractures. The primary consideration for prescribing bisphosphonates to individuals with osteoporosis should continue to be centered on reducing fracture risk, aligning with clinical guidelines. Long-term studies are needed to investigate potential effects on mortality during extended treatment periods. Level I, therapeutic study.

Effect of bisphosphonate and denosumab treatment on TBS in Japanese breast cancer patients with AIBL.

Bisphosphonates and denosumab increase bone mineral density (BMD) for osteoporosis treatment in patients with aromatase inhibitor-associated bone loss (AIBL). This study aimed to directly compare bisphosphonates with denosumab in treating patients with AIBL and to determine the effect of denosumab on the trabecular bone score (TBS). Thirty-nine patients with AIBL receiving osteoporosis treatment (21 in the bisphosphonates group and 18 in the denosumab group) were retrospectively evaluated for changes in lumbar spine and femoral BMD, lumbar spine bone quality (assessed by TBS), and blood bone metabolic markers. The Mann-Whitney and Wilcoxon tests were used for statistical evaluation. After 24months of treatment, the lumbar spine BMD change rate was 5.82 ± 1.10% with bisphosphonates and 10.49 ± 1.20% with denosumab, with the change rate of denosumab significantly increasing over that of bisphosphonates. The change rate in femoral BMD was 2.69 ± 1.16% with bisphosphonates and 2.95 ± 1.26% with denosumab, with no significant difference between the two groups. The rate of decrease in tartrate-resistant acid phosphatase isoform 5b was significantly higher in the denosumab group. The change rate in TBS at 24months of treatment was 0.53 ± 1.26% in the bisphosphonates group and 1.08 ± 1.33% in the denosumab group, with no significant difference between the two groups. After 24months, TBS remained stable. Both bisphosphonates and denosumab may increase BMD, improve bone metabolism, and inhibit bone quality loss in patients with AIBL.

Efficacy of Bisphosphonates in Total Hip Arthroplasty Patients: Systematic Review and Meta-Analysis.

A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A PICOS template was developed to ensure a structured approach. A search for relevant studies was performed across four databases, including Pubmed, Scopus, Embase, and Cochrane. They were all last searched on March 1st and were assessed using the Cochrane risk of bias tool for randomised studies. The final analysis included seven studies with a total of 126 study group participants and 144 control group participants. The studies looked at Bony Mass Density in terms of bone loss on Gruen's femoral zones after THA in a bisphosphonate (treatment) and control group (placebo/no treatment). The analysis revealed a statistically significant difference (p < 0.05) in favour of the bisphosphonate group in many of the included studies at 6, 12, and 24 postoperative months. This systematic review and meta-analysis, using the most recent applicable studies, showed the efficacy of bisphosphonates in limiting periprosthetic osteolysis after THA in a period between 6 and 24 postoperative months. Future studies should focus increasing group sizes and collecting results beyond the 2-year mark.

Bone Augmentation With Alloplastic Graft Material in a Patient Under Bisphosphonate Therapy: A Case Report and Literature Review.

Cases of relatively safe dental implant treatment in patients with low-volume bisphosphonate (BP) have been gradually reported. Although bone augmentation is commonly used when the bone volume is insufficient for implant placement, the studies and case reports regarding the safety of bone augmentation in patients treated with BP remain insufficient. Herein, we report a case wherein bone augmentation was performed after BP treatment with bone healing realized according to imaging, and we review the literature regarding BP and bone augmentation. A 67-year-old Japanese woman requested implant treatment for a hopeless lower right second molar. She had been taking minodronic acid hydrate (50 mg/4 wk) for 18 months to treat steroid-induced osteoporosis. After obtaining informed consent, tooth extraction and bone augmentation within the extraction socket were performed. The tooth was extracted atraumatically to preserve the surrounding alveolar bone, and the extraction socket was intensely curetted. Subsequently, the socket was filled with carbonate apatite granules and covered with a biodegradable membrane, and the wound was sutured without tension. Although protracted wound healing without any symptoms of infection was observed, the wound healed completely. No clinical symptoms were observed, the color of the mucosa at the site was healthy, and imaging findings at 6 months postoperation indicated that osteogenesis had progressed uneventfully.

Goal-directed osteoporosis treatment: ASBMR/BHOF task force position statement 2024.

The overarching goal of osteoporosis management is to prevent fractures. A goal-directed approach to long-term management of fracture risk helps ensure that the most appropriate initial treatment and treatment sequence is selected for individual patients. Goal-directed treatment decisions require assessment of clinical fracture history, vertebral fracture identification (using vertebral imaging as appropriate), measurement of bone mineral density (BMD), and consideration of other major clinical risk factors. Treatment targets should be tailored to each patient's individual risk profile and based on the specific indication for beginning treatment, including recency, site, number and severity of prior fractures, and BMD levels at the total hip, femoral neck, and lumbar spine. Instead of first-line bisphosphonate treatment for all patients, selection of initial treatment should focus on reducing fracture risk rapidly for patients at very high and imminent risk, such as in those with recent fractures. Initial treatment selection should also consider the probability that a BMD treatment target can be attained within a reasonable period of time and the differential magnitude of fracture risk reduction and BMD impact with osteoanabolic versus antiresorptive therapy. This position statement of the ASBMR/BHOF Task Force on Goal-Directed Osteoporosis Treatment provides an overall summary of the major clinical recommendations about treatment targets and strategies to achieve those targets based on the best evidence available, derived primarily from studies in older postmenopausal women of European ancestry.

The impact of foot orthoses on gait in children with Osteogenesis Imperfecta type I, III and IV – a cross-sectional study

BackgroundFor children with Osteogenesis Imperfecta (OI), a rare genetic bone disease, walking can be difficult to carry out due to a combination of bone fragility and deformity, muscle weakness, joint hypermobility, and pain. Bisphosphonate treatment has facilitated more children being able to walk, but for many, foot and ankle hypermobility is a limiting factor. Current evidence on foot orthoses in children with OI is sparse. This study aimed to evaluate gait characteristics in children with OI walking barefoot as compared to walking with foot orthoses.MethodsTwenty-three children with OI and hypermobility (mean age 8.3 ± 3.0 years) were included in this cross-sectional study. Children conducted three-dimensional gait analysis barefoot, and with foot orthoses and appropriate foot wear (stable yet light-weight), respectively. Walking speed, step length, lower limb kinematics and kinetics were collected. Differences in gait characteristics between test conditions were evaluated using paired sample t-tests.ResultsWhen walking with foot orthoses, the external foot progression angle was reduced, peak ankle dorsiflexion angle increased, and peak plantarflexion moment increased as compared to barefoot. No difference was found in walking speed between test conditions, however, children with OI walked with longer steps with foot orthoses as compared to barefoot.ConclusionThe observed gait alterations suggest that foot orthoses, aiming to support the foot and ankle joint, contributed to reduced overall foot rotation as measured by external foot progression, increased peak plantarflexion moment, and increased step length. In a wider perspective, the ability to walk provides the opportunity to be physically active, and thereby increase skeletal loading and prevent fractures, thus, foot orthoses may be an important treatment option to consider in children with OI.Level of evidenceIII.

Assessment of the Admission and Follow-up Characteristics of Children Diagnosed with Secondary Osteoporosis.

Secondary osteoporosis is a condition when the underlying disease or its treatment causes the bone mass to decrease and the bone structure to deteriorate, increasing the risk of fracture. The importance of diagnosis and treatment during childhood and adolescence is due to its long-term negative effects. In this study, our objectives were to determine the diagnostic findings, treatment efficacy, and follow-up characteristics of childhood with secondary osteoporosis. 61 patients diagnosed with secondary osteoporosis between January 2000 and January 2021 were included in the study. The research is a cross-sectional and descriptive study. Study participants had to be under 18 years of age when the primary underlying disease was diagnosed and received treatment for secondary osteoporosis. Patient data were collected from patient files. Patient data were obtained from patient files in hospitals and were interpreted through the IBM SPSS Statistics for Windows version 20.0 (IBM Corp, Armonk, NY, USA). 61 patients (28 women/33 men) were evaluated. The most common underlying primary diseases in patients with secondary osteoporosis were inflammatory diseases (57.7%), neuromuscular diseases (26.2%), immunodeficiency (13.1%), acute lymphoblastic leukemia (8.2%), metabolic diseases (8.2%), and solid organ transplantation. (8.2%), bone marrow transplantation (6.6%) and epilepsy (6.6%). The average chronological age when secondary osteoporosis was diagnosed was 11.89±4.88 years. They were evaluated for osteoporosis 6.39±5.13 years after the onset of the underlying primary chronic diseases. 78.7% of the patients had one or more chronic drug use. Systemic steroid use was 59%, chemotherapeutics 23%, immunomodulatory drugs 19.7%, antiepileptic drugs 8.2%, inhaled steroids 4.9%, IVIG 1.6%, and antituberculosis drugs 1.6%. Additionally, 1.6% of the patients were using testosterone as replacement, 3.3% L-Thyroxine, 1.6% estrogen, and 1.6% growth hormone. Bone pain was detected in 49.2% of the patients. All patients had vertebral fractures before treatment. Bisphosphonate treatment was given to 45 patients with secondary osteoporosis. There was a statistically significant increase in mean bone mineral density (BMD) and bone mineral content values six months after treatment, (p<0.001). There was a significant increase in BMD Z-score values for chronological and height age (p<0.001). The patients' BMD values increased on average by 31.15% with treatment. Following bisphosphonate treatment, there was a significant reduction in both fracture number and bone pain in patients (p<0.01). When patients who received and did not receive steroid treatment were compared, both groups received similar benefits from bisphosphonate treatment. Secondary osteoporosis is a condition that is influenced by many factors, such as the primary disease causing osteoporosis, chronic medication use, especially steroids. If left untreated, osteoporosis leads to important diseases such as bone pain, bone fractures, immobilization, and reduced linear growth of bone. When used to treat childhood secondary osteoporosis, Bisphosphonates significantly improve BMD and reduce fracture risk.

Clinical spectrum of rare bone fragility disorders and response to bisphosphonate treatment: a retrospective study.

Osteogenesis Imperfecta (OI) is a clinically and genetically heterogeneous group of diseases characterized by brittle bones. Though genetic mutations in COL1A1 and COL1A2 account for approximately 85-90% of OI cases, there are now more than twenty genes described, responsible for rare forms of OI. Treatment is based on the use of bisphosphonates and though it is well established that they increase lumbar spine (LS) bone mineral density (BMD), the clinical impact on fracture reduction is still debated.In this study, we investigated the clinical characteristics of 38 patients with a bone fragility disorder that had variants in non-COL1A1/COL1A2 genes in order to study genotype-phenotype correlations, as the natural history of these rare forms is still not well known. We then studied the usefulness of bisphosphonate treatment by evaluating the effects on LS BMD, annual non-vertebral fracture rate, bone turnover markers and height. This study enabled us to better define the natural history of patients with non-COL1 pathogenic variants. Patients with CRTAP and TMEM38B variants consistently had a prenatal presentation with a short (<3rd p) and bowed femur. Importantly, this prenatal involvement does not predict the postnatal severity of the disease. Regarding treatment by bisphosphonates, all patients showed a significant increase in LS BMD while treated and this increase was dependent on the dose received. The increase in LS BMD also translated in a reduction of fracture rate during treatment. Finally, our study showed that the earlier bisphosphonates are initiated, the greater the fracture rate is reduced.

Histological and Histomorphometric illustration the endochondral ossification of the mandibular angle defect repair in rats after oral stimulation with bisphosphonate treatment (an in vivo study)

Background: Bio-phosphonates can be used to lower the risk of hip and spine fractures. Additionally, they can be used to treat Paget's disease of the bones in a variety of dosages. In the procedure that replace hyaline cartilage to bone, this procedure i.e. called endochondral ossification. It starts when mesenchymal cells from the mesoderm develop into chondrocytes. Chondrocytes multiply quickly and release an extracellular matrix to create the cartilage that serves as the model for bone. Objective: To histomorphometric illustration the endochondral ossification of the mandibular angle defect repair in rats after oral stimulation with bisphosphonate treatment. Patients and Methods: 20 rats were used in this work and the animals were divided into the following groups: 10 Rats from the control group. The bone defect was healed naturally without medicament and 10 rats were used in the experiment, and taking the biophosphonate medication helped mend the bone defect. Every single group was studied in 7 and 14 day (5 rats for each healing period) and the surgical procedure was performed for histological and Histomorphometrically examination. The data analysis with spss statistic measure &amp; with P vale (P ≤ 0.05). Results: Active effect of the bio-phosphate medicament in the endochondral ossification and the cell that responsible for the cartilage formation and accelerated the healing of the mandibular defect with inhibition of the bone resoption and finally decrease the time that need to full healing. Conclusion: The chemical medicament that represented by bio-phosphonate accelerated the endochondral ossification in a short time and replacement with bone in the site of the defect.

Histological and Histomorphometric illustration the endochondral ossification of the mandibular angle defect repair in rats after oral stimulation with bisphosphonate treatment (an in vivo study)

Background: Bio-phosphonates can be used to lower the risk of hip and spine fractures. Additionally, they can be used to treat Paget's disease of the bones in a variety of dosages. In the procedure that replace hyaline cartilage to bone, this procedure i.e. called endochondral ossification. It starts when mesenchymal cells from the mesoderm develop into chondrocytes. Chondrocytes multiply quickly and release an extracellular matrix to create the cartilage that serves as the model for bone. Objective: To histomorphometric illustration the endochondral ossification of the mandibular angle defect repair in rats after- oral stimulation with bisphosphonate treatment. Patients and Methods: 20 rats were used in this work and the animals were divided into the following groups: 10 Rats from the control group. The bone defect was healed naturally without medicament and 10 rats were used in the experiment, and taking the biophosphonate medication helped mend the bone defect. Every single group was studied in 7 and 14 day (5 rats for each healing period) and the surgical procedure was performed for histological and Histomorphometrically examination. The data analysis with spss statistic measure &amp; with P vale (P ≤ 0.05). Results: Active effect of the bio-phosphate medicament in the endochondral ossification and the cell that responsible for the cartilage formation and accelerated the healing of the mandibular defect with inhibition of the bone resoption and finally decrease the time that need to full healing. Conclusion: The chemical medicament that represented by bio-phosphonate accelerated the endochondral ossification in a short time and replacement with bone in the site of the defect. Keywords: Bio-phosphonates, Cartilage, Chondrocytes, endochondral ossification.

Changes in serum bone turnover markers and bone mineral density Z-score in children with osteogenesis imperfecta after zoledronic acid treatment.

The study aimed to investigate the changes in the levels of serum bone turnover markers (BTMs) and bone mineral density (BMD) Z-score in pediatric patients with osteogenesis imperfecta (OI) after intravenous bisphosphonate therapy and their association with age and estimated glomerular filtration rate (eGFR). This retrospective study analyzed data from 10 pediatric OI patients treated with intravenous zoledronic acid for over 1 year. Patients' clinical data were collected. The levels of BTMs and BMD Z-score before and after zoledronic acid treatment were analyzed. Significant improvement in BMD Z-score was observed after 6 and 12 months of treatment compared to baseline (all p < 0.05). The N-terminal propeptide of type I procollagen (PINP) levels decreased over time (all p < 0.05), indicating that zoledronic acid treatment decreased bone turnover. The levels of beta-C-terminal telopeptide of type I collagen remained stable after treatment. No correlation was found between PINP level and age, eGFR, or BMD (all p > 0.05). Bisphosphonate treatment can improve BMD and decrease bone turnover (indicated by decreased levels of PINP) in pediatric OI patients. PINP may serve as an independent indicator for monitoring the efficacy of bisphosphonate treatment in pediatric OI patients, particularly in those under the age of 6, where standardized BMD Z-score criteria are lacking.