Atypical Femoral Fracture in an Osteogenesis Imperfecta Patient Successfully Treated with Teriparatide

ObjectiveWe report a case of a successfully healed atypical femoral fracture (AFF) following treatment with teriparatide in a patient with osteogenesis imperfecta (OI). To our knowledge, no successful treatment of AFFs with teriparatide in this subpopulation has ever been described.MethodsThis is a case report of an AFF treated with teriparatide.ResultsThe patient was treated with hormone replacement therapy for 18 years and bisphosphonates for 9 years before suffering a spontaneous AFF in the form of a dislocated noncomminute transverse fracture of the right femoral shaft, and an open reduction and internal fixation (ORIF) with a T2 Femoral Nail was done. Due to nonunion and another fracture distal to the nail, the patient was reoperated on with exchange ORIF and off-label treatment with teriparatide 20 μg/day was started. An X-ray 1 month later showed early signs of fracture healing. A subsequent X-ray 6 months after the last operation showed a solid healing of both right femoral fractures.ConclusionThis is a rare case that highly suggests a potential fracture healing effect of teriparatide treatment and highlights a potential significant practical therapeutic consideration in relation to the management of AFF with delayed healing. (Endocr Pract. 2014;20:e187-e190)     

Atypical femoral fracture in a metastatic bone disease patient six months after discontinuation of denosumab received sequentially to previous bisphosphonate therapy - A case report

Although, both bisphosphonates and denosumab are effective in reducing the risk of skeletal-related events in patients with metastatic bone disease, many concerns were being raised about the possible association between their use and atypical femoral fractures. A case of an atypical femoral fracture in a metastatic bone disease patient, six months after discontinuation of long-term zoledronic acid therapy and sequential treatment with denosumab is reported. After extensive laboratory and imaging examination, the fracture was classified as atypical and it was finally treated with discontinuation of denosumab, long cephalomedullary interlocking nailing and vitamin D administration. Sequential treatment with bisphosphonates and denosumab in patients with metastatic bone disease, may lead to an overlapping treatment effect, increasing bone suppression and the risk of atypical femoral fracture. In addition, discontinuation of denosumab may activate bone remodeling units in an area with microdamage accumulation in cortical bone caused by the previous bone suppression from the antiresorptive treatment. The activation of bone remodeling units may accelerate the occurrence of the atypical femoral fractures.     

Mortality Risk After Atypical Femoral Fracture: A Systematic Review and Meta-analysis

ObjectiveTo summarize all available data using systematic review and meta-analysis to estimate the 1-year mortality risk after atypical femoral fracture (AFF) and risk ratio of mortality after AFF versus typical femoral fracture (TFF).MethodsPotentially eligible studies were identified from MEDLINE and Embase databases from inception to February 2022 using a search strategy that comprised the terms for “atypical femoral fracture” and “mortality.” An eligible study must consist of a cohort of patients with AFF. Then, the study must report the 1-year mortality rate after the AFF or report effect estimates with 95% confidence intervals, comparing the incident mortality between patients with AFF and TFF. Point estimates with standard errors were retrieved from each study and combined using the generic inverse variance method.ResultsA total of 8967 articles were identified. After 2 rounds of independent review by 3 investigators, we identified 7 studies reporting the 1-year mortality rate of AFFs and 3 studies comparing the mortality rate of AFF with that of TFF. Pooled analysis revealed a pooled 1-year mortality rate after an AFF of 0.10 (95% confidence interval, 0.05-0.16; I² = 93.3%). Two studies compared the mortality risks of AFF with those of TFF and revealed conflicting results.ConclusionThe 1-year mortality rate after an AFF was approximately 10%. However, evidence is insufficient to conclude whether there was a difference in mortality risk between AFF and TFF.     

Withdrawal of Denosumab in Patients With Primary Hyperparathyroidism: A Follow-up Report of the DENOCINA Study

ObjectivesWe investigated the development in the primary outcomes: changes in bone mineral density (BMD) measured by dual x-ray absorptiometry at the lumbar spine, total hip, and femoral neck after 2 years.MethodsIn patients with primary hyperparathyroidism, we investigated the effects of 30-mg cinacalcet per day plus 60 denosumab every 6 months for 1 year (Deno group), versus denosumab plus placebo for 1 year (DenoPlacebo-group), versus placebo plus placebo injection for 1 year (Placebo group). After the study’s termination, most patients receiving denosumab were switched to bisphosphonate treatment.ResultsForty-three out of 45 participants were subject to follow-up. A total of 35 patients completed a 2-year follow-up dual x-ray absorptiometry-scan (Deno: n = 13; DenoPlacebo: n = 12; and Placebo: n = 10). None of the groups showed statistically significant changes in BMD or experienced decreases in mean BMD below the study’s baseline level. Overall, the changes in T-scores from the final study measurement to follow-up were similar among the groups (P = .38 for lumbar spine T-score, .63 for total hip, and .97 for femoral neck by 1-way ANOVA). P-calcium was not different over time (P = .20 for change over time and P = .08 for the difference between the groups by repeated measures ANOVA). A total of 5 participants suffered a fracture during the study or follow-up periods, all but one was in the placebo group.ConclusionEvidence suggests that it is possible to at least maintain BMD, and thus potentially lower the fracture risk by a short course of denosumab followed by antiresorptive therapy, where applicable in patients with primary hyperparathyroidism.     

Meta-Analysis of Clinical Fracture Risk Reduction of Antiosteoporosis Drugs: Direct and Indirect Comparisons and Meta-Regressions

ObjectiveAntiosteoporotic drug (AOD) trials have variabilities in duration and fracture risks. This study evaluated AOD’s versus controls regarding reduction in relative rates and rate differences in vertebral and hip fractures and comparative costs.MethodsPrimary randomized controlled trials of antiosteoporotic drugs in postmenopausal women with documentation of vertebral fracture rates or hip fracture rates were extracted from meta-analyses and PubMed through February 2021. Direct and indirect meta-analyses and meta-regressions analyzed the fracture reductions.ResultsThere were 24 randomized controlled trials of drug versus placebo (73 862 women) and 10 randomized controlled trials of drug versus drug. The reductions in the relative rates of vertebral fractures were significant for antiresorptive (alendronate, risedronate, zoledronate, denosumab, and raloxifene) and anabolic (teriparatide, abaloparatide, and romosozumab) drugs. Denosumab, teriparatide, and abaloparatide were more effective in reducing vertebral fracture rates than oral bisphosphates (all P < .05) but were not more effective in reducing vertebral fracture rates than zoledronate. The reductions in hip fracture rates were significant for alendronate, denosumab, and zoledronate (all P < .05), without significant differences among drugs. Anabolic drugs did not show significant hip fracture rate reduction. Meta-regression of rate differences enabled the calculation of costs per vertebral fracture prevented, which were estimated at >$100 000 for anabolic drugs and between $2289 and $28 947 for antiresorptive drugs. Many direct drug versus drug trials were underpowered to demonstrate benefits of one drug over another.ConclusionThis study suggests goal-directed, cost-effective therapies relative to patient risk for vertebral and hip fractures. Anabolic drugs are better at preventing vertebral fractures than oral bisphosphonates. Anabolic drugs are not superior to zoledronate or denosumab and are substantially more expensive. When comparing drugs that prevented hip fractures, there was no statistical benefit of any drug.     

Osteoporosis in Men

ObjectiveTo review information pertinent to bone health and osteoporosis in men.MethodsA review of pertinent literature was conducted.ResultsOsteoporosis affects approximately 2 million men in the US and accounts for an estimated 600,000 fractures each year. There are significant differences in skeletal size and structure between men and women that account for differences in fracture incidence, location, and outcomes. Bone density testing is appropriate for men age 70 and older and younger men (50-69) who have risk factors for osteoporosis. Lifestyle management, including adequate calcium and vitamin D intake, appropriate physical activity, and avoidance of tobacco and heavy alcohol use, is appropriate for all men. Pharmacologic therapy to reduce fracture risk is advisable for men with a clinical diagnosis of osteoporosis (a spine or hip fracture) or a T-score of −2.5 or below in the spine, femoral neck, total hip or 1/3 radius; however, the majority of men at high risk will only be identified using a fracture risk assessment tool, such as FRAX. Alendronate, risedronate, zoledronic acid, denosumab, and teriparatide are Food and Drug Administration (FDA)-approved therapeutic options.ConclusionOsteoporosis in men presents an important public health problem with significant morbidity and mortality. There are recommended strategies for identifying men at high risk of fracture, and effective agents are available for treatment. (Endocr Pract. 2013;19:834-838)     

Anabolic Therapy and Optimal Treatment Sequences for Patients With Osteoporosis at High Risk for Fracture

Objective: Provide an update regarding anabolic medications for osteoporosis, which are often considered to be the last resort for patients with osteoporosis, after multiple fractures have already occurred and other medications have already been administered.Methods: Literature review and discussion.Results: Recent pivotal trial data for anabolic agents and randomized trials comparing anabolic and antiresorptive medications suggest that three anabolic agents (teriparatide, abaloparatide, and romosozumab) reduce nonvertebral and vertebral fractures faster and to a greater extent than potent antiresorptive treatments. Furthermore, bone density accrual is maximized when patients are given anabolic agents first, followed by potent antiresorptive therapy. Since total hip bone density during or after osteoporosis treatment has emerged as an excellent surrogate for future fracture risk, attaining a greater hip bone mineral density is a treatment goal for high-risk osteoporosis patients.Conclusion: This review defines the highest-risk patients and summarizes the rationale for the evolving role of anabolic therapy in the management of postmenopausal women at high risk for fracture.Abbreviations: ACTIVE = Abaloparatide Comparator Trial in Vertebral Endpoints; ARCH = Active Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk; BMD = bone mineral density; FRAME = Fracture Study in Postmenopausal Women with Osteoporosis; FRAX = Fracture Risk Assessment Tool; PTH = parathyroid hormone; TBS = trabecular bone score     

New Treatment Modalities in Osteoporosis

ObjectiveTo describe recently discovered agents for the management of osteoporosis.MethodsA literature review (PubMed search) was conducted to identify agents at various stages of development for osteoporosis treatment. Agents under study or review for approval were included.ResultsIn menopause, bone remodeling is increased, and agents that suppress bone resorption can stabilize bone mass. In contrast, agents that target the osteoblast can increase bone formation and bone mass. Novel antiresorptive agents can target the formation or the activity of osteoclasts. They include denosumab, an antibody to receptor activated nuclear factor kB; new selective estrogen receptor modulators, such as bazedoxifene; and cathepsin K inhibitors, such as odanacatib. Src kinase inhibitors are in the early phases of development. Parathyroid hormone is the only approved anabolic agent for the treatment of osteoporosis. Novel anabolic therapies for osteoporosis may include the use of factors with anabolic properties for bone or the neutralization of growth factor antagonists. Recent discoveries have demonstrated that the Wnt/β-catenin signaling pathway has a central role in osteoblastic cell differentiation. Antibodies to Wnt antagonists, such as sclerostin, are under development as new therapeutic approaches for osteoporosis. Anabolic therapies have the potential to enhance bone mass, but their long-term safety must be proven.ConclusionsNew developments in the treatment of osteoporosis include novel antiresorptive and anabolic agents. Their success will depend on their long-term effectiveness and safety profile. (Endocr Pract. 2010;16:855-863)     

Metabolic bone disease: atypical femoral fractures

Since 2005 reports have been published describing unusual femoral shaft fractures primarily in postmenopausal women treated for prolonged periods with a bisphosphonate drug for osteoporosis. In some patients pain develops in the femur prior to a completed fracture. Bilateral fractures have occurred in some patients. It is unclear whether oversuppression of bone cell activity is a major factor in the pathogenesis of the fractures, or whether these are a rare manifestation of the underlying bone disease. Such fractures do occur in other metabolic bone disorders in which there are marked abnormalities of bone structure.     

A Retrospective Review of Patients with Atypical Femoral Fractures While on Long-Term Bisphosphonates: Including Pertinent Biochemical and Imaging Studies

ObjectiveTo elucidate the effects of prolonged bisphosphonate (BP) exposure on the development of atypical fragility fractures, and to define the associated risk factors.MethodsApproval was obtained from the institutional review board, and a retrospective chart analysis was performed on 51 patients who had been on BPs for at least 3 years and had complete subtrochanteric or diaphyseal femoral fracture(s) between January 2005 and April 2011. All relevant data were available for 25 patients (mean age, 67.52 years). All fractures included in the study were low- or no-energy. Relevant clinical and demographic data were collected regarding age, gender, ethnicity, height, weight, and comorbid medical conditions. Imaging and laboratory data collected on all patients included: calcium, alkaline phosphatase, 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone, serum c-telopeptide, and urine n-telopeptide levels, bone mineral density, radiography, and magnetic resonance imaging.ResultsMost of the patients in this study were Caucasian, were on alendronate, had bilateral findings, and almost half had prodromal symptoms. The 25-OHD level was suboptimal (<30 ng/mL) in 45.8% of the patients. Mean BP duration was 9.84 years, and mean bone density was in the osteopenic, not osteoporotic, range.ConclusionCharacteristics of patients with atypical BP-related fracture include relatively young age, long duration of BP use, suboptimal 25-OHD level, and bone density in the nonosteoporotic range. All of these may be significant risk factors for insufficiency fracture development. (Endocr Pract. 2013;19:456-461)     

Denosumab Use in Adults With Fibrous Dysplasia: Case Reports and Review of the Literature

ObjectiveIn fibrous dysplasia (FD) of the bone, a gain-of-function mutation in the G-nucleotide binding protein alpha subunit results in constitutively active cyclic adenosine monophosphate. Downstream effects include formation of disorganized cortex and bone marrow fibrosis. Patients with FD experience bone pain and are at risk of fracture. Bisphosphonates are traditionally used to manage pain with mixed results. We sought to report denosumab use in patients with FD at our institution and summarized the existing literature on denosumab use in FD.MethodsWe retrospectively identified patients with FD who were treated with denosumab at our institution, describing patient characteristics and outcomes. We reviewed the existing literature on denosumab use in patients with FD.ResultsPatient 1 was diagnosed with FD at the age of 17 years and took bisphosphonates with initial improvement in pain. Pain eventually worsened; therefore, she received 4 doses of denosumab. Patient 2 was diagnosed with FD after a fall and was treated with bisphosphonates, reporting some initial improvement in bone pain. A few years later, the pain recurred, and he received 3 doses of denosumab. Both patients tolerated denosumab well but experienced no improvement in pain. On literature review, although some serious side effects were noted, patients experienced a decline in bone turnover markers, and most reported improvement in bone pain with denosumab.ConclusionDenosumab is a promising therapy for managing symptoms of FD. Further studies are needed to determine the optimal dose and duration of treatment. Its long-term effect on FD lesions remains unclear.     

Switching to Denosumab or Bisphosphonates After Completion of Teriparatide Treatment in Women With Severe Postmenopausal Osteoporosis

ObjectiveTo compare bone mineral density (BMD) changes after 12 months of treatment with denosumab or bisphosphonates in postmenopausal women with severe osteoporosis after stopping teriparatide therapy.MethodsWe retrospectively analyzed 140 postmenopausal women (mean age, 74.2 years) with severe osteoporosis who had been treated with teriparatide for 18 to 24 months at our outpatient clinic in a tertiary endocrine center between 2006 and 2015. After stopping teriparatide therapy, they continued treatment with a bisphosphonate (alendronate, risedronate, ibandronate, or zoledronic acid) or denosumab while receiving daily vitamin D and calcium. BMD at the lumbar spine (LS), total hip (TH), and femoral neck (FN) was measured by dual energy x-ray absorptiometry when teriparatide therapy was discontinued (baseline) and after 12 months of further treatment. Multivariate linear regression models were used to identify the predictors of BMD gain.ResultsAfter stopping teriparatide therapy, 70 women continued treatment with bisphosphonates and 70 received denosumab. LS, but not TH or FN, BMD gain was significantly greater in the denosumab group than in the bisphosphonates group at 12 months. Multivariate analysis showed that BMD gain at the LS was negatively associated with bisphosphonate versus denosumab treatment and positively associated with baseline serum total procollagen type I N-terminal propeptide. BMD gains at the FN were predicted by higher baseline serum urate levels. BMD gains at the TH and FN were negatively associated with pretreatment BMD gains at the same site.ConclusionTwelve months after stopping teriparatide therapy, sequential denosumab treatment appeared to yield higher additional LS BMD gain on average compared with bisphosphonates treatment.     

Comparison Of The Efficacy,Adverse Effects,And Cost Of Zoledronic Acid And Denosumab In The Treatment Of Osteoporosis

ObjectiveInjectable osteoporosis drugs are increasing in popularity due to their efficacy and convenient administration. In this retrospective comparison of the two available treatments, denosumab (Prolia®) and zoledronic acid (ZA, Reclast®), we aimed to determine and compare the efficacy and tolerability of denosumab and ZA.MethodsThe charts of patients who received denosumab and ZA at Loyola Hospital were reviewed, and adverse events were noted. Of primary interest were myalgias, flu-like symptoms, back pain, and fractures. A questionnaire regarding the efficacy, tolerability, and treatment cost supplemented this chart review in a subset of study participants. Bone mineral density (BMD) changes, bone turnover markers, and questionnaire results were also compared.ResultsThe study cohort consisted of 107 patients (51 denosumab, 56 ZA). The denosumab group had a greater mean increase in spine BMD at 1 year (0.060 g/cm²) than the ZA group (0.021 g/cm²; P = .04). The change in femur and spine BMD at 1 year were not significantly different between the 2 groups. The ZA group had a significantly greater incidence of mild flu-like symptoms (29% ZA group vs. 0% denosumab group; P = .04).ConclusionThe denosumab group had a higher mean increase in spine BMD, and the ZA group had a higher incidence of flu-like symptoms, but the study groups were statistically similar in terms of patient satisfaction. As denosumab is still a relatively new therapy, there were a limited number of patients with posttreatment data available for comparison. As more posttherapy data become available, it can be further investigated. (Endocr Pract. 2015;21:275-279)     

Teriparatide as a Systemic Treatment for Lower Extremity Nonunion Fractures: A Case Series

ObjectiveTo investigate the effect of teriparatide (parathyroid hormone [1-34]) on the healing of long bone nonunion fractures.MethodsWe performed a retrospective chart review of patients with fracture nonunion, aged 10 to 99 years who were treated with teriparatide at the Children’s Hospital of Philadelphia or the Hospital of the University of Pennsylvania between November 2002 and January 2013. The primary endpoints were radiographic evidence of callus formation and fracture union, ability to bear weight without affected limb limp, and normal range of motion and strength.ResultsSix patients aged 19 to 64 years with tibial or femoral fractures that had not healed for 3 to 36 months were treated with teriparatide 20 μg/day. Accelerated healing of fracture nonunion was confirmed in 5 of 6 patients with time to complete union of 3 to 9 months. The shortest time to recovery was observed in younger patients without comorbidities. Treatment was well tolerated.ConclusionTeriparatide is a promising treatment for nonunion fractures, but its response depends on associated comorbidities. The potential benefit of teriparatide as an adjunct to treat nonunion justifies randomized placebo-controlled trials to determine its efficacy and safety in broader populations. (Endocr Pract. 2015;21:136-142)     

Iatrogenic Osteoporosis,Bilateral Hip Osteonecrosis,and Secondary Adrenal Suppression in an Hiv-Infected Man Receiving Inhaled Corticosteroids and Ritonavir-Boosted Highly Active Antiretroviral Therapy

ObjectiveTo report the first case of severe osteoporosis associated with a vertebral pathologic fracture and osteonecrosis of femoral heads in an HIV-infected man receiving inhaled corticosteroids and ritonavir-boosted antiretroviral therapy.MethodsWe describe an HIV-infected man with severe osteoporosis, bilateral hip osteonecrosis, and secondary adrenal suppression, including detailed clinical, laboratory, and radiographic data, and review the related literature.ResultsA 60-year-old man with a 15-year history of HIV infection and a medical history of long-standing bronchiectasis treated with inhaled corticosteroids and hypogonadism treated with testosterone was referred to the endocrinology clinic after experiencing an osteoporotic vertebral fracture. He was taking ritonavir-boosted antiretroviral therapy. Osteonecrosis of both hips was also diagnosed, which required total hip replacement therapy.Laboratory evaluation revealed adrenal insufficiency due to increased effect of exogenous inhaled steroids and no other secondary causes of osteoporosis. A bone densitometry study showed osteoporosis of both hips and the lumbar spine. He was treated with intravenous pamidronate. During treatment, he developed bilateral femoral fractures after minor trauma.ConclusionsGiven the potential for increased serum levels of inhaled corticosteroids in patients taking ritonavirboosted highly active antiretroviral therapy, attention must be paid to the risk of bone loss in HIV-infected patients taking inhaled corticosteroids. Prescribing calcium and vitamin D supplementation and considering early osteoporosis screening are reasonable measures for this patient population. Interaction between inhaled corticosteroids and ritonavir may increase risk of hypothalamus-pituitary-adrenal axis suppression. (Endocr Pract. 2011;17:74-78)     

The Emerging Role of Denosumab in the Long-Term Management of Parathyroid Carcinoma-Related Refractory Hypercalcemia

Objective: The main cause of death in patients with parathyroid carcinoma is parathyroid hormone (PTH)-induced hypercalcemia. To date, the management of hypercalcemia has been based on the use of bisphosphonates and calcimimetic agents. In recent reports, the use of denosumab has shown encouraging results in cases of refractory hypercalcemia of malignancy. Our objective is to present a case of successful management of resistant hypercalcemia due to parathyroid carcinoma with denosumab, to review similar cases from the literature, and to propose denosumab's use in the clinical management of PTH-induced refractory hypercalcemiaMethods: Presentation of a case report and review of the literature for cases of parathyroid carcinoma–mediated hypercalcemia successfully treated with denosumab.Results: A 71-year-old man with metastatic parathyroid carcinoma was referred to our department for uncontrolled hypercalcemia, resistant to treatment with bisphosphonates and cinacalcet. Treatment with denosumab (120 mg per month) in addition to cinacalcet (180 mg per day) resulted in normalization of calcium levels and maintenance within the normal range for an observation period of 11 months. Review of the literature revealed 4 case reports and a letter to the editor, all of which reported the successful treatment of resistant hypercalcemia associated with parathyroid carcinoma.Conclusion: Based on the above findings of the effectiveness of denosumab in controlling refractory hypercalcemia, its safety in renal failure and the fact that denosumab may reduce PTH-induced bone loss, we endorse its use in the management of hypercalcemia in patients with parathyroid carcinoma and perhaps other conditions with PTH-induced hypercalcemia.Abbreviations: CT = computed tomography IV = intravenous PTH = parathyroid hormone     

Managing Bone Health in Breast Cancer

ObjectiveOsteoporosis is a common condition that can be caused or exacerbated by estrogen deficiency.MethodsThis narrative review will discuss optimizing bone health in the setting of adjuvant endocrine treatments for hormone receptor–positive breast cancer and the current use of antiresorptive agents as adjuvant therapy and as bone modifying agents.ResultsAdjuvant endocrine treatments for hormone receptor–positive breast cancer (tamoxifen and aromatase inhibitors) affect bone health. The exact effect depends on the agent used and the menopausal state of the woman. Antiresorptive medications for osteoporosis, bisphosphonates and denosumab, lower the risk of bone loss from aromatase inhibitors. Use of bisphosphonates as adjuvant treatment in breast cancer, regardless of hormone receptor status, is increasing because of benefits seen to cancer relapse and survival.ConclusionOptimizing bone health in women with breast cancer during and after cancer treatment is informed by an understanding of breast cancer treatment and its skeletal effect.     

An Interesting Case of Peripheral Vascular Disease,Vascular Reperfusion,and Subsequent Development of Pain Due to Paget's Disease of Bone

ObjectiveTo present a case of Paget’s disease of bone that was unmasked after vascular reperfusion.MethodsIn this case study, we review the presentation, evaluation, diagnosis, and management of a patient with Paget’s disease and peripheral vascular disease.ResultsA 79-year-old-woman with a history of coronary artery heart disease and recent finding of a T5 compression fracture was hospitalized for evaluation of right lower extremity claudication. Angiography demonstrated a focal complete occlusion of the distal right femoral and popliteal arteries. A self-expanding stent was placed in the distal femoral and popliteal arteries. Approximately 48 hours after the procedure, the patient developed severe, right lower leg pain. On endocrine evaluation, the patient was found to have clinical signs suggesting Paget’s disease of bone, which was subsequently confirmed by imaging.ConclusionThis patient’s development of severe pain following reperfusion of distal femoral and popliteal arteries is in keeping with the known and aforementioned hypervascularity of pagetic bone. The finding of increased warmth over an area of skeletal deformation should always raise the possibility of Paget’s disease of bone.(Endocr Pract. 2013;19:e61-e63)     

髓腔内固定联合低强度脉冲超声对兔股骨中段骨折愈合作用研究

摘要 目的：针对髓腔内固定联合低强度脉冲超声对兔股骨中段骨折愈合作用进行研究。方法：选择成年兔股骨中段骨折40只,作为本次的研究对象,将其平均分为对照组和观察组。所有兔子,在手术前禁水、禁食,对其右后肢进行备皮,称重、麻醉,对照组实施髓腔内固定治疗,观察组实施髓腔内固定联合低强度脉冲超声治疗。治疗后1、2、3、4周对兔子的骨折部位进行影像学检查确定兔子的骨折线模糊情况,并在各周采集样品进行组织学检查。治疗4周后对骨折愈合情况进行检查。结果：观察组愈合程度I级、II级、II级比例均低于对照组相应比例,差异具有统计学意义（P＜0.05）,观察组IV级、V级比例分别为35.0 %、55.0 %,均高于对照组的5.0 %、5.0 %,差异具有统计学意义（P＜0.05）;观察组兔子的在1 w、2 w、3 w、4 w骨折线模糊程度评分高于对照组相应时间评分,差异具有统计学意义（P＜0.05）。结论：在兔股骨中断骨折治疗中,实施髓腔内固定联合低强度脉冲超声,可以提高骨折的愈合速度,加速骨折修复,整体治疗效果显著,可以在临床上进行推广实施。     

Long-Term Follow-up of patients on Drug Holiday from Bisphosphonates: Real-World Setting

ObjectiveAtypical femoral fractures and osteoporosis of the jaw have been associated with prolonged bisphosphonate therapy for postmenopausal osteoporosis. American Association of Clinical Endocrinologists guidelines suggest a drug holiday after 4 to 5 years of bisphosphonate treatment for moderate-risk patients and 10 years for high-risk patients, but there are minimal data on safe holiday durations. A recent U.S. Food and Drug Administration perspective suggests a treatment duration of 3 to 5 years. Our aim was to describe a group of patients on drug holiday and identify fracture risk.MethodsA retrospective chart review was conducted of 209 patients who started a bisphosphonate drug holiday between 2005 and 2010. Collected data included bone mineral density (BMD), markers of bone turnover, vitamin D status, and clinical and radiographic reports of fractures.ResultsEleven of 209 patients (5.2%) developed a fracture. Their mean age was 69.36 years (±15.58), and the mean lumbar spine and femoral neck T-scores were −2.225 (±1.779) and −2.137 (±0.950), respectively. All patients had a significant increase in bone-specific alkaline phosphatase at 6 months, which was more pronounced in the fracture group (3.0 ± 0.6083 μg/L vs. 1.16 ± 1.9267 μg/L). Over 4 years, there was no significant change in mean lumbar spine BMD for the entire cohort, but there was a statistically significant decline in the femoral neck BMD at year 2 (−0.0084 ± 0.03 gm/cm²).ConclusionThe current practice of initiating BP holidays needs further evaluation, particularly in the real-world setting. Elderly patients and those with very low BMD warrant close follow-up during a drug holiday. A fracture, early significant rise in bone turnover markers, and/or a decline in BMD should warrant resumption of osteoporosis therapy. (Endocr Pract. 2013;19:989-994)