An Audit of the effect of Bone Morphogenetic Protein-2 Treatment in patients with non-union of long bone fractures.

OBJECTIVE: To evaluate the outcomes, clinical and radiological application of Bone Morphogenetic Protein-2 alone versus Bone Morphogenetic Protein-2 with autograft in long bone non-unions. METHODS: A prospective review of patients was done with fracture non-union admitted to Aga Khan University Hospital, Karachi, from January 2016 to January 2019. The patients were divided into two groups; those exposed to Bone Morphogenetic Protein-2 alone in group 1, and those exposed to Bone Morphogenetic Protein-2 plus autologous graft in group 2. RESULTS: Background characteristics of both the groups were analysed. Patients were followed up at 6, 12 and 24 weeks through their medical records. The primary outcome was postoperative union at 6, 12 and 24. Union was defined by having the clinical union as well as the radiological union at the same time of assessment. Of the 80 patients enrolled, 13(16.25%) were excluded, and 5(6.25%) were lost to follow-up. The final sample had 62(77.5%) patients; 35(56.5%) in group 1, and 27(43.5%) in group 2. Union at 6 weeks was observed in 13(21%) patients; 8(62%) in group 1, and 5(38%) in group 2. Union at 12 weeks was observed in 38(61%) patients; 20(53%) in group 1, and 18(47%) in group 2. CONCLUSIONS: Results showed that using the adjuvant treatment alone was not worse than using it along with bone autologous graft.

Teriparatide as an Effective Nonsurgical Treatment for a Patient with Basicervical Peritrochanteric Fracture Nonunion-A Case Report.

The nonunion rate of surgically treated basicervical peritrochanteric fractures has been reported to be as high as 9%. Due to the high 1-year mortality rate following revision surgery, finding an effective nonsurgical treatment option is of interest. Over the last decade, numerous reports have been published that have suggested teriparatide as an effective treatment for certain types of fracture nonunion. However, the literature focused on teriparatide treatment for proximal femoral fracture nonunion is scanty. A 70-year-old man suffering from a left hip basicervical peritrochanteric fracture received cephalomedullary nail fixation. Nine months after the surgery, the patient still complained of left hip pain referring to the medial thigh with an antalgic limping gait. No sign of healing was noted for more than a consecutive 3 months of follow-up. Fracture nonunion was diagnosed and further confirmed by the computed tomography (CT). The patient preferred nonsurgical treatment after thorough discussion. He then received 4 months of subcutaneous teriparatide injections, 20 mcg daily. After less than 4 months of teriparatide treatment, a follow-up CT confirmed fracture union and the patient's pain subsided. The patient also tolerated independent ambulation afterward. Teriparatide has been reported to be an effective treatment for certain types of fracture nonunion. Our case goes a step further to expand its possible application for basicervical peritrochanteric fracture nonunion. However, further larger scale studies are needed to confirm its efficacy.

Successful treatment for bilateral femoral neck insufficiency fractures: a rare lesion case report and an updated review of the literature.

BACKGROUND: The incidence of insufficiency fracture (IF) at femoral neck is low, accounting for about 5% of all insufficiency fractures, and IF at bilateral femoral neck is less common with more occurrence in athlete or serviceman. With the aging of populations, more cases of bilateral femoral neck IF have occurred recently, while the standard clinical treatment still remains lacking due to the complexity of these patients. CASE PRESENTATION: A 55-year-old male patient complained pain in his bilateral hip, with no history of trauma, glucocorticoid hormone consumption or radiotherapy, and imaging examination revealed fracture nonunion and shortening in his left femoral neck, and double fracture line on the right femoral neck. The patient received a cementless THA for the left femoral neck fracture and conservative treatment for the right side, followed by Elcatonin injection and oral administration of Carbonate D3 Granules. After 4 months of fellow-up, the patient presented improved functional scorings in bilateral hip joints, with no signs of prothesis infection or loosening. CONCLUSION: We present a rare case of bilateral femoral neck IF in a middle-aged male and the treatment is successful. The timely CT and MRI examinations of bilateral hip joints for patients was necessary for orthopedists to select proper therapeutic regimen. In addition, the choice for therapeutic regimen of bilateral femoral IF should not only be based on the professional judgement of orthopedists, but also on the wishes of patients.

MiR-539-5p negatively regulates migration of rMSCs induced by Bushen Huoxue decoction through targeting Wnt5a.

Bone fractures are very common, and above 5% of the fractures are impaired, leading to nonunions and severe disablilities. The traditional Chinese medicine Bushen Huoxue decoction (BHD) has been used to treat fracture in China. Our previous report has found that BHD promotes migration of rat mesenchymal stem cells (rMSCs) by activating Wnt5a signaling pathway. However, whether and how miRNAs are involved in modulating rMSCs migration induced by BHD has not been explored. In the present study, miRNA microarray analysis and further validation by real-time quantitative RT-PCR revealed that miR-539-5p was down-regulated in BHD-induced rMSCs. Transfection of miR-539-5p mimics suppressed rMSCs migration while the miR-539-5p inhibitor promoted rMSCs migration. Our results suggested that miR-539-5p was a negative regulator of migration of rMSCs induced by BHD. Target prediction analysis tools and Dual-luciferase reporter gene assay identified Wnt5a as a direct target of miR-539-5p. MiR-539-5p inhibited the expression of the Wnt5a and its downstream signaling molecules including JNK, PKC and CaMKII, which played a critical role in regulating migration of rMSCs. Taken together, our results demonstrate that miR-539-5p negatively regulates migration of rMSCs induced by BHD through targeting Wnt5a. These findings provide evidence that miR-539-5p should be considered as an important candidate target for the development of preventive or therapeutic approaches against bone nonunions.

Therapy of aseptic nonunions with parathyroid hormone.

The absence of osseous consolidation of a fracture for 9 or more months with no potential to heal is defined as nonunion. Both for the patient and from a socioeconomic point of view, nonunions represent a major problem. Hypertrophic, vital nonunions are distinguished from atrophic avital ones. Risk factors for a delayed fracture healing are insufficient immobilisation, poor adaptation of the fracture surfaces or residual instability, interposition of soft tissue within the fracture gap, as well as circulation disturbances and infections. The incidence of nonunions after fractures of the long bones lies between 2.6 and 16% depending on the surgical technique used. In human and animal studies, a positive effect of parathyroid hormone (PTH) on fracture healing has been shown. PTH has a direct stimulatory effect on osteoblasts and osteoclasts. In addition, it appears to influence the effect of osseous growth factors. In this prospective study, 32 patients with nonunions were treated with teriparatide to investigate the effects of PTH on fracture healing. Definitive healing of the nonunions following PTH treatment could be observed in 95% of the cases.

Clinical application of bone morphogenetic proteins for bone healing: a systematic review.

PURPOSE: This paper documents the existing evidence on bone morphogenetic proteins (BMPs) use for the treatment of bone fractures, non-union, and osteonecrosis, through a review of the clinical literature, underlying potential and limitations in terms of cost effectiveness and risk of complications. METHODS: A systematic review was performed on the PubMed database using the following string: (bone morphogenetic proteins OR BMPs) and (bone repair OR bone regeneration) including papers from 2000 to 2016. The search focused on clinical trials dealing with BMPs application to favor bone regeneration in bone fractures, non-union, and osteonecrosis, in English language, with level of evidence I, II, III, and IV. Relevant data (type of study, number of patients, BMPs delivery material, dose, site, follow-up, outcome, and adverse events) were extracted and analyzed. RESULTS: Forty-four articles met the inclusion criteria: 10 randomized controlled trials (RCTs), 7 comparative studies, 18 case series, and 9 case reports. rhBMP-2 was documented mainly for the treatment of fractures, and rhBMP-7 mainly for non-unions and osteonecrosis. Mixed results were found among RCTs and comparative papers: 11 reported positive results for BMPs augmentation, 3 obtained no significant effects, and 2 showed negative results. The only study comparing the two BMPs showed a better outcome with rhBMP-2 for non-union treatment. CONCLUSION: Clinical evidence on BMPs use for the treatment of fractures, non-union, and osteonecrosis is still controversial, with the few available reports being mainly of low quality. While positive findings have been described in many studies, mixed results are still present in the literature in terms of efficacy and adverse events. The difficulties in drawing clear conclusions are also due to the studies heterogeneity, mainly in terms of different BMPs applied, with different concomitant treatments for each bone pathology. Therefore, further research with well-designed studies is needed in order to understand the real potential of this biological approach to favour bone healing.

Is Parathyroid Hormone A Viable Solution For Nonunion? A Systematic Review And Pooled Analysis.

We conducted a systematic review and pooled analysis of published studies to evaluate the clinical results of parathyroid hormone (PTH) in the treatment of nonunion and delayed union and assess whether there are any adverse effects of PTH. Four electronic databases (PubMed, Web of Science, EMBASE, and Cochrane library) were searched from 1950 to 2016. A total of 24 patients from 13 published studies were identified. The mean age of the patients was 57 years (range, 19-91 years). Mean duration of nonunion after initial treatment (surgical or conservative) was 8.4 months (range, 3-36 months). PTH was given to the patients for 1.5 months to 10 months (mean, 5.3 months) for various types of fractures. The union rates after using PTH was 96%. Mean time to union after PTH therapy was 7.3 months (range, 3-15 months). No patients reported any side effects during the entire period of PTH treatment. Our study has helped to further elucidate the outcomes of PTH therapy in the treatment of nonunion. We believe that PTH is a viable option that is a promising, safe, and effective anabolic treatment for delayed union and nonunion.

Treatment of Infected Forearm Nonunions With Large Complete Segmental Defects Using Bulk Allograft and Intramedullary Fixation.

PURPOSE: The purpose of this study is to report the results of a series of infected forearm nonunions treated from 1998 to 2012 using a staged reconstruction technique. METHODS: At a median of 42 months follow-up, 7 patients who had an average segmental defect of 4.9 cm (range, 2.3-10.4 cm) were available for clinical and radiographic evaluation. Treatment consisted of serial debridement, implantation of an antibiotic cement spacer, and staged reconstruction using a bulk radius or ulna allograft with intramedullary fixation. RESULTS: All 7 patients ultimately achieved solid bone union, although 4 patients (57%) required additional surgery, consisting of autologous bone grafting and plating, to achieve healing at 1 of the allograft-host junction sites. No patient had recurrence of infection, and all reported substantial improvement with increased function and decreased pain. CONCLUSIONS: Our approach ultimately resulted in a 100% union rate without recurrence of infection, although many patients may require additional surgery to attain healing at both allograft-junction sites. Using bulk allograft provides the ability to span a large defect while reconstituting the forearm anatomy. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

The effect of rhBMP-2 in a novel, non-instrumented extremity nonunion model.

BACKGROUND: Pre-clinical models of bony nonunion typically employ critical-length defects. However, these models may not accurately reflect clinical practice since many nonunions are diagnosed without bone loss. We developed a non-displaced rat ulna fracture model in order to examine the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) with an absorbable collagen sponge (ACS) for nonunion treatment. METHODS: Transverse diaphyseal ulna fractures were created in 24 Sprague-Dawley rats. Eight animals (Group 1: Nonunion) received no further intervention. The remaining 16 animals were treated with 5 µg rhBMP-2/ACS at 8 weeks after the original intervention (Group 2: Nonunion + BMP) or at the time of initial injury (Group 3: Fresh fracture + BMP). RESULTS: In Group 1, 7 of 8 fractures demonstrated gross motion and a persistent radiographic gap (12.5% healing rate). In Groups 2 and 3, fractures healed at a rate of 75% (6 of 8 in each group) as determined by manual and radiographic evaluation. Biomechanical testing for torque load-to-failure and torsional stiffness demonstrated no significant difference between healed specimens treated with rhBMP-2. CONCLUSIONS: To our knowledge, this is the first description of a physiologic, non-stabilized, non-defect fracture nonunion model in a rodent. Furthermore, unlike previous nonunion models, the healing rates after treatment with rhBMP-2 are comparable to that of clinical data, suggesting that this model may provide an environment more representative of nonunions in humans.

A method of treatment for nonunion after fractures using mesenchymal stromal cells loaded on collagen microspheres and incorporated into platelet-rich plasma clots.

PURPOSE: There is evidence showing that mesenchymal stromal cells (MSC) may constitute a potential therapeutic strategy to induce bone regeneration. In this work, we investigate the capacity of autologous bone marrow (BM) MSC loaded on collagen microspheres (CM) and included into autologous platelet-rich plasma (PRP) clots (MSC/CM/PRP) to induce bone formation in patients with nonunion lesions. METHODS: MSC were isolated from BM cells of patients with nonunion lesions. Phenotypical (marker expression) and functional studies (osteogenic differentiation) were performed. MSC were seeded on CM and included into autologous PRP clot (MSC/CM/PRP). The capacity of MSC/CM/PRP to induce bone formation was evaluated in three patients diagnosed with nonunion. RESULTS: MSC loaded on CM/PRP clots maintain their biological functions, in vitro. After three months, post-MSC transplantation, all patients showed evidence of osteogenesis at the site of nonunion. After one year, all patients showed a complete healing of the nonunion. CONCLUSIONS: Our results support the use of autologous MSC transplanted as MSC/CM/PRP for the treatment of nonunion fractures. Future studies incorporating a larger number of patients may confirm the results obtained in this work.

Teriparatide as a systemic treatment for lower extremity nonunion fractures: a case series.

OBJECTIVE: To investigate the effect of teriparatide (parathyroid hormone [1-34]) on the healing of long bone nonunion fractures. METHODS: We 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. RESULTS: Six 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. CONCLUSION: Teriparatide 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.

Effective treatment of delayed union of a lumbar vertebral fracture with daily administration of teriparatide in a patient with diffuse idiopathic skeletal hyperostosis.

INTRODUCTION: We herein describe a case of delayed union of a lumbar spine fracture in a 70-year-old patient with diffuse idiopathic skeletal hyperostosis (DISH). CLINICAL COURSE AND RESULT: Because he decided not to undergo surgical treatment, we provided conservative treatment with teriparatide (TPTD). Union was obtained in 2 months, and no adverse events were observed during treatment. Six months after starting the TPTD, further bone formation was observed and the lumbar instability had resolved. CONCLUSION: This is the first report of successful use of TPTD to treat delayed union of a spine fracture in a patient with DISH without surgical intervention.

A rhPDGF-BB/bovine type I collagen/ß-TCP mixture for the treatment of critically sized non-union tibial defects: An in vivo study in rabbits.

Non-union during healing of bone fractures affects up to ~5% of patients worldwide. Given the success of recombinant human platelet-derived growth factor-B chain homodimer (rhPDGF-BB) in promoting angiogenesis and bone fusion in the hindfoot and ankle, rhPDGF-BB combined with bovine type I collagen/ß-TCP matrix (AIBG) could serve as a viable alternative to autografts in the treatment of non-unions. Defects (~2 mm gaps) were surgically induced in tibiae of skeletally mature New Zealand white rabbits. Animals were allocated to one of four groups-(1) negative control (empty defect, healing for 8 weeks), (2 and 3) acute treatment with AIBG (healing for 4 or 8 weeks), and (4) chronic treatment with AIBG (injection 4 weeks post defect creation and then healing for 8 weeks). Bone formation was analyzed qualitatively and semi-quantitatively through histology. Samples were imaged using dual-energy X-ray absorptiometry and computed tomography for defect visualization and volumetric reconstruction, respectively. Delayed healing or non-healing was observed in the negative control group, whereas defects treated with AIBG in an acute setting yielded bone formation as early as 4 weeks with bone growth appearing discontinuous. At 8 weeks (acute setting), substantial remodeling was observed with higher degrees of bone organization characterized by appositional bone growth. The chronic healing, experimental, group yielded bone formation and remodeling, with no indication of non-union after treatment with AIBG. Furthermore, bone growth in the chronic healing group was accompanied by an increased presence of osteons, osteonal canals, and interstitial lamellae. Qualitatively and semiquantitatively, chronic application of AI facilitated complete bridging of the induced non-union defects, while untreated defects or defects treated acutely with AIBG demonstrated a lack of complete bridging at 8 weeks.

Teriparatide treatment of a glucocorticoid-associated resorbing nonunion of a type III odontoid process fracture: a case report.

STUDY DESIGN: This is a unique case report. OBJECTIVES: To describe a successful case of Teriparatide treatment of odontoid nonunion. SUMMARY OF BACKGROUND DATA: Animal models suggest that this drug may enhance fracture healing, and there are 3 similar cases previously published elsewhere. METHODS: We describe the evolution of our case over time with serial computed tomography scan imaging confirming the treatment success. RESULTS: Drug treatment of the odontoid nonunion was successful. CONCLUSION: Drug treatment of the odontoid nonunion may be an option and merits formal study.

Use of bone morphogenetic protein-2 (rh-BMP-2) in treatment of wrist and hand nonunion with comparison to historical control groups.

The purpose of this study is to report the percentage of patients achieving union, time to union, and complications with the use of bone morphogenetic protein-2 (rh-BMP-2) in surgical repair of established nonunion in the hand and wrist. Twenty-seven patients with nonunion of the hand and wrist were treated between 2005 and 2011 with surgical repair and augmentation using 4.2 mg of rh-BMP-2. Sites of nonunion included the phalanx (seven), carpus (nine), distal radius (five), and distal ulna (six). Radiographic union and complications were the primary and secondary outcomes, respectively. Eighty-nine percent (24/27) of patients achieved union within an average of 4.3 ± 2.8 months of surgery. There were no direct complications from administration of rh-BMP-2. Radiographic union was consistent with published rates for nonunion repair of scaphoid, phalanx, and distal radius fractures. Rh-BMP-2 did not produce superior rates of union in the patients with wrist and hand nonunion.

Atrophic femoral nonunion successfully treated with teriparatide.

Teriparatide is a synthetic polypeptide hormone that contains the 1-34 aminoacid fragment of the recombinant human parathyroid hormone. It has been approved for the treatment of postmenopausal women with osteoporosis who are at high risk for sustaining a fragility fracture. It has been shown that teriparatide also accelerates fracture healing by improving the biomechanical properties of the fracture callus, increasing endochondral ossification and bone remodeling in animal models. This effect has been observed in several case reports. Fracture healing disorders negatively affect the patient's quality of life and result in high healthcare costs, as a second surgery is required to stabilize the fracture and stimulate bone biology. Future biotechnologies that accelerate fracture healing may be useful tools. We present a case report of delayed union of a femoral fracture treated with teriparatide. She was diagnosed with right distal metaphyseal femoral fracture on total knee arthroplasty. She underwent surgery at our center consisting of ORIF with lateral femoral locking plate in October 2011. Radiologic controls at 5 and 7 months did not show any signs of healing. After 2 months of treatment with teriparatide, the X-ray showed the presence of bone bridges and a decreased gap between fragments and a different aspect of neoformed bone. After 3 months of treatment, healing was complete. Our case report seems to confirm the possible effect of TPTD as bone induction through a more rapid healing of fractures. The TPTD could have a potentially important role in treating some forms of nonunion and delay in consolidation. Thus, one could hypothesize the possibility of a medical treatment with TPTD both as a preventive way and also as a support to the synthesis in high risk of nonunion fractures and complexed fractures in osteoporotic bone.

Bone Morphogenic Protein for Upper Extremity Fractures: A Systematic Review.

BACKGROUND: This review discusses success, time to healing, and complications of bone morphogenic proteins (BMPs) 7 and 2 in treating upper extremity nonunions. METHODS: Systematic review identified 26 of 479 studies that met inclusion criteria. Publications described application of BMPs to acute and chronic upper extremity delayed unions/nonunions. Unions, complications, patient demographics, and fracture/healing patterns were pooled and analyzed. RESULTS: Nonunions treated with BMP-7 (n=302) involved the humerus (64%), forearm (22%), clavicle (11%), and hand/wrist (3%), with prior surgical correction attempted in 84%. Nonunions treated with BMP-2 (n=96) involved the humerus (58%), hand/wrist (27%), forearm (14%), and clavicle (1%), with prior surgical correction attempted in all. Most nonunions (80%) were present for over 12 months before BMP application. Union rates of BMP-7 varied according to site: hand/wrist (95%), humerus (74%), forearm (29%), and clavicle (6.2%) nonunions achieved union as defined by study authors in 232 days (confidence interval=96-369, Q<0.001) on average. While not significant across studies, BMP-2 union rates were 71% of hand/wrist and 75% of humerus nonunions. Comparison of the BMPs demonstrates different proportions of success in humerus and hand/wrist fractures (P<.001) but not forearm fractures (P<.77) and longer time to radiographic union with BMP-7 (P<.011). CONCLUSIONS: Most hand/wrist and humerus nonunions treated with BMP-7 and BMP-2 achieved union, with significant similarity among BMP-7 studies not observed in BMP-2 studies. Nonunions treated with BMP-7 have longer healing times yet similar complication rates compared with BMP-2. Overall, BMPs are an effective adjunct to fracture healing with acceptable complication profile.

Long-Term Assessment of Bone Regeneration in Nonunion Fractures Treated with Compression-Resistant Matrix and Recombinant Human Bone Morphogenetic Protein-2 in Dogs.

OBJECTIVE: The aim of this study was to assess bone density, bone architecture and clinical function of canine nonunion distal appendicular long bone fractures with a defect treated with fixation, compression-resistant matrix and recombinant human bone morphogenetic protein-2 (rhBMP-2). STUDY DESIGN: Prospective cohort study with dogs at least 1-year post treatment. Computed tomography was performed and quantitative measurements from previous fracture sites were compared with measurements from contralateral limbs. Subjective evaluation included gait assessment and palpation. RESULTS: Six patients met the inclusion criteria. The rhBMP-2 treated bone exhibited higher density at the periphery and lower density in the centre, similar to the contralateral limb. All patients were weight bearing on the treated limb and all fractures were healed. CONCLUSION: The rhBMP-2-treated bone underwent restoration of normal architecture and density. Acceptable limb function was present in all patients. The results of this study can serve as a basis for long-term response in treating nonunion fractures in veterinary patients.

Antibiotic cement-coated rigid locked nails in infected femoral and tibial nonunion. Reoperation rates of commercial versus custom-made nails.

INTRODUCTION: The objective of this study is to assess bone union, infection control, and reoperation rates in a series of patients with infected femoral or tibial nonunion treated with antibiotic-cement-coated rigid nails and to compare the results obtained with custom-made nails versus commercial nails. METHODS: We retrospectively analyzed a series of consecutive patients with infected nonunion of the femur or the tibia treated with antibiotic-cement-coated rigid nails between January 2010 and 2020. We assessed patients' distinctive characteristics, initial injury, type of nail used (custom-made nail with vancomycin or commercial nail with gentamicin), success rate (bone union + infection control), reoperation rate, and failure rate. Comparative analyses were conducted between reoperated and non-reoperated patients regarding the type of nail used. A multivariate regression analysis was performed to assess the risk variables that impacted reoperation rates. RESULTS: We included 54 patients with 22 (40.74%) infected femoral nonunions and 32 (59.25%) tibial nonunions, who were treated with 38 (70.37%) custom-made antibiotic-cement coated nails and 16 (29.62%) commercial nails. Bone union and infection control were achieved in 51 (94.44%) cases. The reoperation rate was 40.74% (n = 22), and the failure rate was 5.55% (n = 3). The use of custom-made nails was associated with a higher risk of reoperation (Odds Ratio 4.71; 95% Confidence Interval 1.10 - 20.17; p = 0.036). CONCLUSION: Antibiotic-cement-coated nails reached a 94.44% success rate. Nails manufactured in the OR coated with vancomycin cement were associated with a higher risk of reoperation than commercial nails loaded with gentamicin cement. LEVEL OF EVIDENCE: III comparative, observational, non-randomized.

Teriparatide, a nonsurgical solution for femoral nonunion? A report of three cases.

We medicated teriparatide in three patients, who had a nonunion of the femur even after the initial surgical intervention. Teriparatide was administered for 3-9 months after a diagnosis of nonunion. A successful union was obtained in all three patients without further surgical intervention, and no adverse events related to the use of teriparatide were observed. Our report showed that teriparatide could be an alternative to surgical intervention in nonunion of the femur.