Recurrent Fractures Research Articles

Қазақтандағы жетілмеген остеогенезі бар балаларды хирургиялық емдеуде отандық интрамедуллярлық телескопиялық жүйенің күтілетін үлесі

Osteogenesis imperfecta (OI) is a group of inherited connective tissue disorders in collagen structure, processing or cross-linking, new bone formation and osteoblast differentiation, which result in fragility of the bones, recurrent fractures and deformities.The article presents scientific data on the types and features of metal structures used in intramedullary osteotomy performed for the surgical treatment of fractures and deformities of long tubular bones with osteogenesis imperfecta in children and outlines the benefits of the developed domestic intramedullary telescopic system "DOSSANOV" in providing surgical treatment to children with osteogenesis imperfecta. For the "crystal children", whose number is growing in Kazakhstan, the expected advantages of using this system are analyzed.Key words: Osteogenesis imperfecta, children, intramedullary osteosynthesis, osteotomy, intramedullary rods, intramedullary telescopic system.

Anterior Shoulder Instability in a Young Individual with Concomitant Coracoid Process Fracture Treated with the Latarjet Procedure – A Rare Case Report

Coracoid fracture occurs with shoulder instability due to direct humeral head impaction. Incidence coracoid fracture with shoulder dislocation is rare amounts to 0.8-2%. We encountered clinical challenge of unique combination of both shoulder instability and coracoid fracture. This technical note will describe the treatment of the same. A 23-year-old male suffering from recurrent shoulder dislocation sustained coracoid fracture. Further evaluation showed glenoid defect of 25%. Magnetic resonance study showed on track lesion with Hill-Sach lesion of 9 mm, labral defect anteriorly with no associated rotator cuff tear. The patient was managed with open Latarjet procedure with fracture coracoid fragment with conjoint tendon as graft. Our purpose of reporting this technical note is to provide an option of dealing both instability and coracoid fracture in single sitting and usage of coracoid fractured fragment as an excellent graft of choice in acute presentation. However, certain limitations such as adequacy of graft in size and shape do exist operating surgeon which must be aware of the same.

Retracted: Analysis of Influencing Factors of Medication Compliance in Patients with Recurrent Vertebral Fractures after Percutaneous Kyphoplasty and the Role of Family-Centered Education Intervention.

[This retracts the article DOI: 10.1155/2021/3974674.].

Biallelic frameshift variants in PHLDB1 cause mild-type osteogenesis imperfecta with regressive spondylometaphyseal changes

BackgroundOsteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders characterised by susceptibility to fractures, primarily due to defects in type 1 collagen. The aim of this study is to...

Clinical spectrum and diagnostic challenges of vitamin D dependent rickets type 1A (VDDR1A) caused by CYP27B1 mutation in resource limited countries

Vitamin D dependent rickets type 1A (VDDR1A) is a rare autosomal recessive condition due to inactivating mutation of CYP27B1. It mimics clinically, biochemically and rediologically to nutritional and hypophosphatemic rickets. In developing countries like Pakistan, VDDR1A is often misdiagnosed as nutritional rickets or hypophosphatemic rickets due lack of free access to 1,25 (OH) 2 D level and genetic testing. This study was aimed to determine the clinical spectrum and diagnostic challenges of VDDR1A due to CYP27B1 mutation in developing countries. Retrospective review of all cases of VDDR1A due to CYP27B1 mutation over a period of two years presenting in the Pediatric Endocrine clinic of Hameed Latif Hospital, Lahore, Pakistan. Six cases of VDDR1A (4 males) were identified. Mean age of clinical manifestation was 14 (9-24) months. Mean age of presentation to endocrine department was 5.5 (1.5-11.8) years. Growth failure and bony deformities were the most common presentation (n=6), followed by repeated diarrheas and abdominal distension (n=3) and recurrent fractures (n=1). All cases shared same biochemical profile of low/normal calcium, hypophosphatemia, raised alkaline phosphatase, raised PTH, normal/high 25(OH)D and tubular reabsorption of phosphate (TRP) <85%. Patients treated with calcitriol showed rapid healing as compared to those treated with 1-alfacalcidol. We should have a high index of suspicion of VDDR1A in rickets not responding to cholecalciferol therapy.

Mutation and Phenotype Analysis in Patients with Osteopetrosis Caused by Loss-of-Function Mutation of &amp;lt;I&amp;gt;CLCN7 &amp;lt;/I&amp;gt;Single Allele

Objective: To investigate the relationship between gene mutation and clinical phenotype in patients with autosomal dominant osteopetrosis type 2 (ADO2) caused by single allele mutation of <I>CLCN7</I>. Methods: The two ADO2 cases were clinically described in detail, <I>CLCN7</I> gene were screened by the next generation sequence assay, and validated by Sanger method. The hazard of mutations was evaluated on PolyPhen2 website. Literature review helped to browse and gather ADO2 cases with <I>CLCN7</I> data, accordingly all found <I>CLCN7</I> mutant loci were mapped on the peptide chain, and clinical presentations in each case were tentatively summarized corresponding gene mutation. Phenotype was classified as mild type, intermediate type and severe type according to the degree of clinical presentation. Mild type presents mainly with bone and/or joint pain and occasional bone fracture, intermediate type with additional multiple and recurrent bone fracture, sever type with hematopoietic dysfunction in addition to recurrent bone fractures. Results: The first case was a 30 year old man presenting as mild ADO2 with shorter stature than familial hereditary height, as well as back pain and knee joint pain for up-to nine years. The second case was a 13 year old boy who suffered from recurrent bone fractures since four years ago in addition to short stature and more severe bone pain, but had normal peripheral blood picture. His prominent bone change showed by X-Ray indicated a more typical and severe osteopetrosis than the former. Gene analysis indicated a mutation of c.2284C>T (E24), p.R762W in the first case and c.856C>T (E10), p.R286W in the second case. Literature review gathered 42 pathogenic mutations, mild, intermediate and severe clinical type account for 33.3%, 46.7% and 20.0%, respectively. Among family members of probands, 58.8% had unaffected mutation-carrier, and 44.7% had family history of the disease. Conclusions: In spite of single allele inactivation, <I>CLCN7</I> related ADO2 may cause highly various clinical phenotype of osteopetrosis, covering normal unaffected, mild, intermediate and severe conditions. The relationship between genotype and phenotype remains obscure in the disease.

Risk Factors for First and Recurrent Fractures among Kidney Transplant Recipients.

Introduction: Kidney transplantation is associated with increased risk of bone fracture. Current literature reports widely variable fracture burden and contains limited data on risk factors for recurrent fractures. Methods: The incidence of all and major osteoporotic fractures (hip, forearm, thoracolumbar, and proximal humerus) were assessed. The risk factors for first and recurrent fractures among 1285 Canadian kidney transplant recipients transplanted between January 1, 2004, and December 31, 2013 were also identified. Results: The 10-year cumulative incidence of all fractures and major osteoporotic fractures in this population was 27.1% (95% CI: 22.5, 32.4) and 17.8% (95% CI: 13.4, 23.5), respectively. On multivariable analysis, female sex (HR = 1.64 [95% CI: 1.20, 2.26]), history of fracture (HR = 1.54 [95% CI: 1.12, 2.11]), and pretransplant diabetes (HR = 1.85 [95% CI: 1.29, 2.65]) were recipient factors found to increase the risk for any first fracture posttransplant. These risk factors persist in analysis with the time origin 3-months posttransplant, where transplant age (HR = 1.01 [95% CI: 1.00, 1.03]) and increased time on pretransplant dialysis (HR = 1.06 [95% CI: 1.00, 1.12]) also emerge as risk factors for first fracture. On multivariable shared frailty model analysis, increased risk of recurrent fractures was associated with recipient female sex (HR = 1.74 [95% CI: 1.21, 2.51]) and history of diabetes (HR = 1.76 [95% CI: 1.17, 2.66]). Discussion: The results suggested that some risk factors for first fracture may not inform risk of recurrent fractures. As such, fracture risk should be assessed accordingly to optimize long-term care and implement preventive measures.

Ossa rotte e diagnosi difficili

The Author describes the case of a 5-year-old boy with recurrent bone fractures without blue sclera eventually diagnosed as osteogenesis imperfecta due to a mutation in BMP1 gene.

Comparing the Fracture Profile of Osteosarcopenic Older Adults with Osteopenia/Osteoporosis Alone.

To determine whether osteosarcopenia is associated with a greater likelihood of recurrent fractures, as well as type of fracture, than osteopenia/osteoporosis or sarcopenia alone. Anthropometry (height/weight; scales and stadiometer), body composition (bone mineral density [BMD] and appendicular lean mass; dual-energy x-ray absorptiometry), grip strength (hydraulic dynamometer), and gait speed (4m) were measured in an outpatient clinic. WHO definition for osteopenia/osteoporosis (BMD T-score below -1 SDs) while sarcopenia was defined by SDOC or EWGSOP2. Number and location of fractures within the past 5years were self-reported and verified by medical records (unverified fractures excluded). Univariable and multivariable regressions were used to examine the association between the exposure and outcome while adjusting for confounders. 481 community-dwelling older adults (median age: 78, IQR: 72, 83; 75.9% women) were included. Prevalence of osteosarcopenia depended on the definition (SDOC: 179 (37.2%); EWGSOP2: 123 (25.6%)). In multivariable analysis adjusting for age, sex, alcohol, smoking, BMI, lowest BMD T-score, physical activity, and comorbidities, the likelihood of recurrent fractures (≥ 2 vs 0-1) was significantly higher in those with osteosarcopenia versus osteopenia/osteoporosis irrespective of the definition (SDOC: odds ratio [OR]: 1.63, 95% CI: 1.03, 2.59, p = 0.037; EWGSOP2: OR: 1.83, 95% CI: 1.12, 3.01, p = 0.016]. Associations with sarcopenia alone (SDOC: 10; EWGSOP2: 7) were not possible due to the extremely low prevalence of this condition in those with normal BMD. Our data suggest osteosarcopenia is associated with a greater likelihood of recurrent fractures versus osteopenia/osteoporosis alone. Further studies are needed to evaluate the relationship with sarcopenia alone.

Correlation between psoas muscle area and contralateral hip fracture after intertrochanteric fracture

To investigate the relationship between the area of psoas major muscle(PMI) and recurrent contralateral hip fracture in the initial intertrochanteric fracture. Total of 87 patients with intertrochanteric fracture of femur from January 2008 to January 2011 were selected for CT scanning of lumbar spine and hip at the time of the first fracture, and then divided into two groups according to whether there was fracture in the contralateral hip, 13 patients in the contralateral hip fracture group, 5 males and 8 females, aged(82.30±5.66) years;there were 74 cases in the non contralateral hip fracture group, including 32 males and 42 females, with an age of (79.70±5.84) years. The gender, age, preoperative blood albumin value, operation side, body mass index(BMI), Harris score of hip joint one year after operation, Barthel index before operation and medical diseases before operation were observed and compared between two groups. The PMI was used to compare the area of psosa major on CT before operation in two groups, and the correlation between the area of PMI at the time of initial fracture and the fracture of the contralateral hip was evaluated. The two groups were followed up for more than 2 years after operation. There was a significant difference in PMI between two groups(P<0.05). There was a significant positive correlation between preoperative PMI and the time of re fracture of the contralateral hip(r=0.641, P=0.018). There are differences in the area of PMI in patients with contralateral hip fracture, so the area of PMI can be regarded as an important risk factor for contralateral hip fracture.

Risk factors of primary and recurrent fractures in postmenopausal osteoporotic Chinese patients: A retrospective analysis study

BackgroundAs postmenopausal osteoporotic fractures can cause higher rates of disability and mortality in women; it is essential to analyze the factors associated with primary and recurrent fractures in postmenopausal osteoporosis (PMOP) patients.MethodsRetrospective analysis of 2478 PMOP patients aged ≥ 50 years who attended the Shanghai General Hospital from January 2007 to December 2016, including 1239 patients with no fractures and 1239 patients with histories of fractures (1008 in the primary fracture group and 231 in the re-fracture group). All patients' basic clinical data, serum biochemical and bone metabolic markers, bone mineral density (BMD), and other indicators were recorded uniformly. Comparing the differences between the clinical characteristics of patients with primary and recurrent fractures, as well as the differences in the clinical characteristics of patients with primary and recurrent fractures in combination with different diseases, further analyses the risk factors for primary and recurrent fractures in PMOP patients. SPSS.26 was used for statistical analysis.ResultsCompared to the unfractured group, the fractured group was older and had lower height and bone mineral density (all P < 0.01), with the re-fractured group having lower BMD at each key site than the primary fracture group (all P < 0.01). Analysis of the combined disease subgroups showed that serum BGP levels were lower in the primary and re-fracture patients with diabetes than in the non-diabetic subgroup (P < 0.05), and serum CTX levels were lower in the re-fracture group with diabetes than in the primary fracture group with diabetes (P < 0.05). Patients with recurrent fractures with cardio-vascular diseases had lower BMD than the subgroup without cardio-vascular diseases (P < 0.05) and also had lower BMD than the group with primary fractures with cardio-vascular diseases (P < 0.05). Multiple logistic regression analysis showed that advanced age, overweight, low lumbar spine and total hip BMD were risk factors for primary and recurrent fractures; and comorbid chronic liver and kidney diseases were risk factors for primary fractures.ConclusionPMOP patients with advanced age, overweight, low bone mineral density, and comorbid chronic liver and kidney diseases are at greater risk of fractures and require early intervention to reduce fractures occurrence. Moreover, those who are elderly, overweight, and have low bone density should also be aware of the risk of re-fractures.

An Orthopaedic Surgeon Led Osteoporosis (OSLO) Model of Care reduces early recurrent fracture rates and improves treatment compliance in patients treated for osteoporotic fractures.

This study aims to evaluate the efficacy of an Orthopaedic Surgeon Led Osteoporosis Model of Care (OSLO-MoC) as compared to a Case Manager Led Osteoporosis Model of Care (CMLO-MoC) in reducing early osteoporotic re-fracture rates and treatment compliance in patients. This was a single centre, retrospective, comparative cohort study of all patients screened and treated for secondary osteoporotic fracture prevention from the 2008 to 2018 at an orthopaedic surgical unit. From the 2008 to 2013, patients were recruited under the CMLO-MoC and from 2014 to 2018, under the OSLO-MOC. Logistics regression analysis was used to identify significant predictors such as OSLO-MOC implementation, gender, ethnicity, marital status and education level for patient recruitment, treatment compliance and secondary fracture rates at 12-month follow-up. Over a 10-year period, 7388 patients were screened of which 2855 patients were eligible for analysis. A total of 1234 patients were recruited under CMLO-MoC and 1621 patients under OSLO-MOC. Implementation of the OSLO-MOC was associated with greater patient recruitment, OR 1.26 (95%CI 1.06-1.49, P = 0.007). Of the 2855 patients recruited, OSLO-MOC implementation, OR 2.61 (95%CI 2.03-3.36, P < 0.001), and a higher level of education, OR 1.428 (95%CI 1.02-1.43, P = 0.037), were associated with improved compliance to medication at 12months. OSLO-MOC implementation was the only factor associated with reduced risk of secondary fractures at 12months, OR 0.14 (95%CI 0.03-0.66, P = 0.013). The OSLO-MOC has shown to be effective in reducing the rate of re-fracture and osteoporotic medication initiation and compliance of patients. IV.

Zoledronic acid for osteoporosis and associated low-energy fractures

Zoledronic acid is a third-generation amino-containing BF that has been used to treat patients with osteoporosis for more than 15 years. Over the years, numerous experimental and clinical studies have proven the high efficacy of the drug in osteoporosis, both in women of various age groups, and in men, with primary and secondary osteoporosis, in patients with varying degrees of bone loss and risk of fractures. Intravenous infusions of zoledronic acid have been shown to result in a rapid gain of bone mass, a significant reduction in the risk of low-energy fractures of the vertebrae (spine), proximal femoral and nonvertebral fractures on the whole. However, in recent years, the use of the drug has significantly decreased, which is associated both with the lack of awareness of primary care physicians about the possibilities of this drug, and the fear of such complications of its use as atypical fractures and osteonecrosis of the jaw bones. The presented review aims to increase the knowledge of physicians regarding the mechanism of action of zoledronic acid, the regimens for prescribing the drug in various forms of osteoporosis and fractures against its background. The given clinical example shows the ability of zoledronic acid (osteostatics) to increase the mass of not only cancellous, but also the cortical bone of the proximal femur, which increases the role of zoledronic acid in the prevention of recurrent fractures. On top of that, the prolonged effect of the drug allows, when the desired therapeutic effect is achieved, to reduce the frequency of prescribing according to the ‘drug holiday’ principal, decreasing economic expenditures and medical and social burden.

Analysis of clinical efficacy after PKP in patients of different genders.

To investigate the clinical efficacy of Percutaneous Kyphoplasty (PKP) in male and female patients. The clinical data of patients treated with PKP in our hospital from January 2018 to October 2020 were analyzed retrospectively. These patients were divided into female group and male group according to gender differences. The visual analogue scale (VAS) and activity function score (LAS) were recorded before operation, immediately after operation and 1 year after operation, and postoperative complications such as cement leakage and recurrent vertebral fracture were recorded. The above observation indexes between the 2 groups were statistically compared. A total of 171 patients (118 in female group and 53 in male group) were included. There was no other difference between the 2 groups except that thoracic vertebral fracture was more common in women (P < .05). The VAS of female group and male group were (7.14 ± 0.61) and (7.11 ± 0.51) before operation, (3.05 ± 0.66) and (2.89 ± 0.64) after operation, 1 year after operation (1.10 ± 0.50) and (1.02 ± 0.37). There was no difference in each period between the 2 groups (P > .05). But there was a significant decrease after operation, which was recognized between the 2 groups (P < .05); The activity scores of female group and male group were (3.08 ± 0.48) and (3.07 ± 0.43) before operation, (1.86 ± 0.42) and (1.85 ± 0.50) after operation, 1 year after operation (1.01 ± 0.92) and (1.02 ± 0.14). There was no difference in each period between the 2 groups (P > .05). But there was a significant decrease after operation, which was recognized between the 2 groups (P < .05). Postoperative cement leakage was revealed in 21 cases (12.28%), 16 cases (13.56%) in female group and 5 cases (9.43%) in male group, which was no significant difference between the 2 groups. During the 1-year follow-up, postoperative recurrent vertebral fracture was revealed in 4 cases (2.34%), 2 cases (1.69%) in the female group and 2 case (3.77%) in the male group, which was also no significant difference between the 2 groups. Patients treated with PKP can immediately get pain relief and activity function improvement. PKP is a safe and effective minimally invasive surgery for both female and male patients.

Current Strategies to Control Recurrent and Residual Caries with Resin Composite Restorations: Operator- and Material-Related Factors

This review addresses the rationale of recurrent and/or residual caries associated with resin composite restorations alongside current strategies and evidence-based recommendations to arrest residual caries and restrain recurrent caries. The PubMed and MEDLINE databases were searched for composite-associated recurrent/residual caries focusing on predisposing factors related to materials and operator's skills; patient-related factors were out of scope. Recurrent caries and fractures are the main reasons for the failure of resin composites. Recurrent and residual caries are evaluated differently with no exact distinguishment, especially for wall lesions. Recurrent caries correlates to patient factors, the operator's skills of cavity preparation, and material selection and insertion. Material-related factors are significant. Strong evidence validates the minimally invasive management of deep caries, with concerns regarding residual infected dentin. Promising technologies promote resin composites with antibacterial and remineralizing potentials. Insertion techniques influence adaptation, marginal seal, and proximal contact tightness. A reliable diagnostic method for recurrent or residual caries is urgently required. Ongoing endeavors cannot eliminate recurrent caries or precisely validate residual caries. The operator's responsibility to precisely diagnose original caries and remaining tooth structure, consider oral environmental conditions, accurately prepare cavities, and select and apply restorative materials are integral aspects. Recurrent caries around composites requires a triad of attention where the operator's skills are cornerstones.

ODP629 A Case of Juvenile Onset Hypophosphatasia Diagnosed In An Elderly Patient With Recurrent Fractures.

Abstract Background Hypophosphatasia (HPP) is a rare genetic disorder characterized by defective bone mineralization. Here we report a case of juvenile onset HPP in an elderly man. CASE A 77-year-old man presented for management of osteoporosis. He complained of joint pains and trouble walking. He had recurrent non-traumatic fractures since his teenage years and he and his sister were diagnosed with childhood rickets. He sustained fractures of both forearms, right ankle, right hip and left femoral neck, and had undergone right hip replacement and left femoral neck internal fixation. In his 20's, following a MVA he had several tooth extractions and eventually required dentures. He was misdiagnosed with osteogenesis imperfecta, vitamin D deficient osteomalacia and pseudogout, and had been treated with cholecalciferol and alendronate in the past. On exam, we noted a waddling gait, short stature and bowing of his knees. Labs revealed normal vitamin D 25-OH 48 ng/mL (30-100), and PTH 18 pg/mL (14-64), borderline corrected calcium 10.5 mg/dL (8.4-10.6) and elevated phosphorous 4.4 mg/dL (2.2-4.3). ALP was notably low 30 U/L (40-150) and had ranged between 15-46 U/L since 2009. These findings caught our attention and we ordered Vitamin B6 levels which were elevated &amp;gt;250. 0 ng/mL (2.1-21.7). Genetic testing identified two ALPL gene variants, a rare C.340G&amp;gt;A variant and a c.571G&amp;gt;A variant which has been found to be causative of HPP. His DXA scan showed normal L-spine (T-score 3.3) and significantly decreased BMD of the proximal 1/3 of the left forearm (T-score -4.4). Hip and femur were not assessed due to presence of hardware. He is scheduled to start treatment with Asfotase alfa. Conclusion HPP is caused by ALPL gene mutations, which lead to loss of function of the enzyme tissue nonspecific alkaline phosphatase (TSNALP). Clinical manifestations such as seizures, recurrent fractures and premature dental loss are observed. Pseudogout may occur due to intraarticular calcium pyrophosphate deposition, as in our patient. Characteristic lab findings are elevated metabolites of TNSALP, including urine inorganic pyrophosphate (PPi) and serum pyridoxal 5'phosphate (PLP) (biologically active metabolite of vitamin B-6). A persistently low ALP is most suggestive and may be a clue for early referral. Genetic testing is confirmatory, but novel mutations may be missed. Delayed diagnosis in our patient led to increased morbidity, potentially avoidable surgeries and inappropriate treatment with bisphosphonate which are contraindicated as they may increase risk for atypical fractures. Asfotase alfa is a TNSALP enzyme replacement therapy designed to address the underlying cause of HPP and studies show improvement in bone mineralization, fracture healing, decreased concentration of PLP and PPi, and improved physical function and quality of life. Cost and availability remain a barrier to many patients. Presentation: No date and time listed

PSAT157 Efficacy of Bisphosphanate Treatment in Pediatric Patients with Osteoporosis Due to Immobilization

Abstract Introduction Osteoporosis is medical condition commonly associated with immobilization in children, which can lead to a vicious cycle of disability, worsening osteoporosis, and recurrent fractures. Currently, bisphosphonates are widely used as a standard therapy in children with osteoporosis, but there are limited data on efficacy according to its dosage and duration. We aimed to evaluate efficacy of bisphosphonate treatment according to the dosage and duration in pediatric patients with osteoporosis due to immobilization.METHOD: We reviewed medical records of pediatric patients who were diagnosed with osteoporosis due to immobilization rated as Gross Motor Function Classification System (GMFCS) grade V, and who received bisphosphonate therapy with regular check-up for at least 1 year. The dosage and duration of the treatment, biochemical laboratory measurements, data of bone densitometry, and the occurrence of side effects were collected. Results Subjects were 21 children. The average duration of bisphosphonate treatment was 2.0 ± 0.9 years, and mean cumulative dose per body weight of bisphosphonate was 7.7 ± 2.5 (mg/kg/year). After the treatment, mean lumbar spine bone mineral contents (BMC) significantly increased from 14.20 ± 8.58 (g) to 19.38 ± 9.89 (g) (p&amp;lt;0.05), lumbar spine bone mineral density (BMD) significantly increased from 0.40 ± 0.14 (g/cm2) to 0.49 ± 0.14 (g/cm2) (p&amp;lt;0.05), and height-adjusted lumbar spine BMD Z-score also showed improvement from -2.66 ± 1.66 to -1.66 ± 1.38 with statistical significance (p&amp;lt;0.05). The cumulative dose and the duration of treatment were not related to its efficacy, but increasing average dose per body weight in each cycle (mg/kg/cycle) showed significant effects on increasing change in height-adjusted lumbar spine BMD z-score (β = 1.065, p &amp;lt;0.05). Discussion BMC, BMD, and height-adjusted BMD z-score significantly increased after bisphosphonate treatment in pediatric patient with osteoporosis due to immobilization. Independent of cumulative dosage and duration, the efficacy of bisphosphonate treatment increased significantly as average dose per body weight in each cycle increased. Further studies with sufficient number of subjects and long term follow-up observation are needed. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

RF30 | PSAT138 Romosozumab-aqqg in the Treatment of Osteoporosis in a Patient with Hypophosphatasia

Abstract Background Hypophosphatasia (HPP) is a rare inherited condition that causes osteomalacia and recurrent fractures. Therapeutic options for osteoporosis in patients with concomitant HPP are limited due to concerns for a greater likelihood of atypical femoral fractures (AFF) with anti-resorptive agents such as bisphosphonates and denosumab. We present a patient with HPP and OP who was treated with the anti-sclerostin antibody romosozumab-aqqg (Romo). Clinical Case An 81-year-old female was referred for management of OP. Fracture history included a hip fracture around age 40, and bilateral metatarsal fractures around age 65. Her initial DXA scan at age 57 showed osteoporosis at the lumbar spine (LS, T-score: -2.8) and femoral neck (FN, T-score -3.2). Sequential osteoporosis treatment over the subsequent 20 years included several years of oral bisphosphonates, hormone replacement therapy, teriparatide for one year followed by two years of alendronate, and one denosumab injection. Despite almost 20 years of pharmacologic osteoporosis treatment, her bone mineral density (BMD) worsened. HPP was suspected on the basis of low serum alkaline phosphatase (AP) levels ranging from 25-37 U/L (ref: 35-104 U/L). The diagnosis was substantiated by an elevated plasma vitamin B6 level of 305 mcg/L (ref: 5-50 mcg/L) and confirmed by genetic testing showing a diagnostic missense mutation c.571G&amp;gt;A in exon 6 in the ALPL gene. After diagnosing HPP, her osteoporosis was treated with an additional year of teriparatide followed by raloxifene, which she tolerated poorly. Following two years of expectant management, during which time her BMD worsened despite calcium and vitamin D supplementation to T-scores of –4.4 at the LS, she was started on Romo. After 11 monthly injections, a follow up DXA scan showed improvements of 21%, and 10% at the LS and total hip, respectively. These changes were substantially greater than what she experienced with her first year of teriparatide therapy (+4% and +8%, respectively). Blood AP remained low on Romo (37 IU/L and 29 IU/L at 9 and 12 months post-Romo initiation). She tolerated Romo and well and experienced no fractures during treatment. Discussion Management of osteoporosis in patients with HPP is challenging, as bisphosphonates and denosumab are generally avoided due to concern for an increased risk of AFF. Case reports of patients with HPP have suggested good BMD response to teriparatide. To our knowledge, this is the first report of a patient with HPP and osteoporosis treated with Romo. In our patient, Romo did not significantly impact serum AP, but improved BMD significantly more than in response to teriparatide. In conclusion, Romo is a potential treatment option for OP in patients with HPP for whom limited alternatives exist. Optimal osteoporosis treatment following a 1-year course of Romo remains to be determined. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:05 p.m. - 1:11 p.m.

PMON20 Snyder Robinson Syndrome: A Rare Syndrome

Abstract Introduction Snyder Robinson Syndrome (SRS) is a rare X-linked intellectual disability disorder caused by inactivating mutation in the spermine synthase (SMS) gene which is involved in polyamine biosynthesis. It was first described by Snyder and Robinson in 1969 and so far about 20 cases have been reported worldwide. The affected males have short stature, slender build with asthenic habitus, hypotonia, facial dysmorphism with a prominent lower lip, kyphoscoliosis, broad-based gait, osteoporosis with frequent fractures, developmental delay, seizures, and speech and motor disability. Hypotonia presents during the neonatal period and the developmental delay and facial dysmorphism are manifested within the first year of life. Osteoporosis develops within the first decade of life resulting in fractures in the absence of trauma or after minor trauma. No formal diagnostic criteria have been established for Snyder Robinson syndrome. The diagnosis is made based on clinical presentation and biochemical testing of spermine synthase enzyme activity. It is confirmed by molecular genetic testing by identification of a hemizygous loss-of-function SMS pathogenic variant. Currently there is no treatment guideline for Snyder Robinson syndrome. Speech, physical, and occupational therapy can be helpful for intellectual and developmental disability. Kyphoscoliosis is treatment per standard management by orthopedics and surgery is recommended for cleft lip. Calcium supplementations are used for osteoporosis to prevent recurrent fractures. The role of bisphosphonates for osteoporosis is controversial with no proven benefit or effectiveness in Snyder Robinson syndrome. Anti-seizure medications are recommended for seizures along with Neurology follow-up, though some affected individuals may have drug-resistant seizures. Case Presentation A 32-year-old male presented to the Endocrinology clinic as a new patient with his mother. He was referred by his primary care physician for monitoring of calcium. He had a past medical history of Snyder Robinson Syndrome. He had genetic testing in the past which showed mutation in the spermine synthase (SMS) gene. He was a thin man with a BMI around 19 kg/m2. He had intellectual disability, facial dysmorphism, kyphoscoliosis, abnormal gait, speech and motor disability. He had a history of seizures, but was currently not on any anti-seizure medications. He had a history of low bone density for age and history of fractures. He was taking calcium and multivitamin supplementation. He was seen by the physical medicine and rehabilitation department for physical and occupational therapy. Conclusion Although rare, Snyder Robinson syndrome should be suspected in males with intellectual disability, hypotonia, asthenic habitus with the diminished body bulk, bone abnormalities, facial dysmorphism, motor and speech disability, and seizures. The number of patients would increase in the future with the increasing use of genetic testing in patients who present with undefined developmental abnormalities. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Romosozumab-aqqg in the Treatment of Osteoporosis in a Patient With Hypophosphatasia

Hypophosphatasia is a rare, inherited condition that causes osteomalacia and recurrent fractures. Therapeutic options for osteoporosis in patients with hypophosphatasia are limited because of concerns for a greater likelihood of atypical femoral fractures with antiresorptive agents. We report here the case of a patient with hypophosphatasia and osteoporosis who was treated with romosozumab-aqqg (Romo). An 81-year-old woman presented for management of osteoporosis with multiple fractures. She experienced a decline in bone mineral density over 20 years despite sequential osteoporosis treatment with oral bisphosphonates, hormone replacement therapy, teriparatide, and denosumab. Hypophosphatasia was suspected because of low serum alkaline phosphatase levels and was confirmed by genetic testing. After diagnosing hypophosphatasia, bone mineral density continued to decline and a trial of Romo was begun. After 1 year of Romo therapy, bone mineral density improved by 21%, and 10% at the lumbar spine and total hip, respectively. These changes were substantially greater than what she had experienced with prior teriparatide therapy. Blood alkaline phosphatase remained low on Romo. To our knowledge, this is the first report of a patient with hypophosphatasia and osteoporosis treated with Romo. In our patient, Romo did not significantly impact serum alkaline phosphatase, but improved bone mineral density significantly. In conclusion, Romo is a potential treatment option for osteoporosis in patients with hypophosphatasia for whom limited alternatives exist.