THE RISK OF ITERATIVE FRACTURES IN PATIENTS WITH OSTEOGENESIS IMPERFECTA - CASE REPORT

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1 Rev. Med. Chir. Soc. Med. Nat., Iaşi 2017 vol. 121, no. 1 SURGERY CASE REPORTS THE RISK OF ITERATIVE FRACTURES IN PATIENTS WITH OSTEOGENESIS IMPERFECTA - CASE REPORT D. Popescu 1*, B. Puha 1, B. Veliceasa 1, S. Gheorghevici 2, O. Alexa 1 Grigore T. Popa University of Medicine and Pharmacy Iasi Faculty of Medicine 1. Department of Surgery (II) 2. Sf. Spiridon County Clinical Emergency Hospital Iași *Corresponding author. dragospopescu1975@yahoo.com THE RISK OF ITERATIVE FRACTURES IN PATIENTS WITH OSTEOGENESIS IM- PERFECTA-CASE REPORT (Abstract): Osteogenesis imperfecta is characterized by connective tissue involvement and is due to quantitative and qualitative changes of collagen type I. The curative treatment is not possible, but the introduction of antiresorptive bisphosphonate therapy and multidisciplinary approach of this pathology has allowed a considerable improvement in quality of life for these patients. The case presented is of a patient who inherited the disease from the paternal side and has a very rich medical history represented by the existence of 18 fractures. Leg fracture occurred at the age of 20 years has not been treated with centromedullary implants due to the accentuated tibial curves and tibial medullary canal obliteration, so osteosynthesis with plate was don. Removal of osteosynthesis material 18 months postoperatively resulted in the emergence of iterative fracture after 3 months, n e- cessitating a reintervention by the same technique with bone consolidation. Keywords: BLUE SCLERA, COLLAGEN, BONE FRAGILITY, OSTEOSYNTHESIS. Osteogenesis imperfecta (O.I.) is a hereditary disease which involves the connective tissue and is due to quantitative and qualitative changes of collagen type I. The clinical expression of this alteration of connective tissue can be various, but manifests most commonly by fragility of the bone associated with multiple fractures and deformities of anatomical segments, blue stained sclera, impairment of the internal ear segment with disturbing of hearing to complete extinction, developmental abnormalities of the teeth. The disease was detected beginning with the 17 th century and was originally classified by Silence (1), based on clinical and radiological modifications, in four types and later, with the introduction of molecular genetics techniques, classification has been extended to 8 main types. The most frequently encountered are the type I and IV. Type I is characterized by the mildest clinical manifestation. The transmission of the disease is usually autosomal dominant (80-90%) but an autosomal recessive transmission is also possible, even an appearance of a spontaneous mutations that make possible its emergence in the absence of a family history. Prenatal diagnosis is possible in case of risk pregnancies in the weeks 10-12, by analyzing the collagen produced by fetal cells, interruption of pregnancy being a 157

2 D. Popescu et al. good option in this case, considering the poor prognosis of these children. The fetal ultrasound is the second diagnostic method, as it can visualize the fractures already established (2). Clinical manifestations can vary from simple osteopenia to fractures in utero and are those who raise the suspicion diagnosis, the genetic analysis being the diagnosis of certainty. Most patients fall into type I and most often the stature is normal, distortions are minimal and the intellect is unaffected. Type II is a form that is manifested soon after birth and often incompatible with life. Type III and IV have a more severe clinical expression than type I and are characterized by triangular faces, short stature and important bony deformities. The peculiarity specific for type V is represented by the interosseous membrane calcification in forearm and fractures healing by hypertrophic calluses. The disease affects both sexes in equal proportions, all races and ethnic groups being exposed (3), and has an estimated incidence of 6-7 cases per 100,000 people worldwide (4) of which about half are affected with OI type I or IV (5). The first 4 types of the disease are due to mutations of collagen type I alpha 1 chain (COL1A1) and collagen type I alpha 2 chain (COL1A2). Bone fragility is due to decreased amount of collagen type I. Patients of types V to IX show mutations in cartilage associated protein gene (CRTAP), prolyl 3-hydroxylase 1 (LEPRE1), peptidylprolyl isomerase B (PPIB) and FK506 binding protein 10 (FKBP10) genes. Although curative treatment is not possible, multidisciplinary approach of this pathology has allowed a considerable improvement in quality of life. The introduction of antiresorptive bisphosphonate therapy resulted in a considerable reduction in the number of fractures and their further complications (6). The correction of deformities by orthopedic techniques, the maintenance of joint mobility through physical therapy, introducing modern analgesic medication, are other important therapeutic resources (7). CASE REPORT The patient, female aged 20 years is taken in our evidence starting with July 2014, when she was presented after a minor right leg injury. Radiological examination revealed a fracture of both bones of the right leg in the distal part and a particular aspect of them represented by a thin structure of both tibia and fibula, deformation of skeletal parts by accentuated curves and post fracture sequels, disappearance of spinal peroneal canal and narrowing until the obliteration of the tibial canal, a marked osteoporosis especially in the ankle and foot (fig. 1). Fig. 1. Fracture in distal part of right leg The patient's medical history included a total of 18 fractures, with onset around the age of 1 year, when the first fracture of the lower limbs occurred and was suspected of osteogenesis imperfecta, diagnosis made in the context of a family history. The disease 158

3 The risk of iterative fractures in patients with osteogenesis imperfecta - case report had a paternal transmission, patient s grandfather experiencing a mild form of the disease and presenting a normal waist without having suffered any fractures, and who, besides the existence blue whites, installed hearing problems after the age 40 years. In her father's case, the disease evolved more aggressively, due to the emergence of 6 fractures before puberty and their end after the age of 14. He also has been affected by hearing disorders occurred after age 23 years. In the father's family, the disease manifested in a different form in his sister also, who developed hearing impairment around the age of 20 years, while fractures occurred in adulthood, after 35 years. The patient's sister also presents the characteristics of the disease, but in a mild form, suffering only one fracture until now. Physical examination reveals a waist of 146 cm and a weight of 39 kg. The patient presents blue sclera and slight modifications of the dentition. Musculoskeletal examination shows the hyperlaxity of articulations in both upper and lower limbs as well as an inequity of 4 cm length between the lower limbs due to underdevelopment of the left femur that was installed after its fracture at the age of 9 years, probably by affecting the cartilage of growth. Thorax examination reveals the presence of kyphoscoliosis, without generating breathing difficulties or auscultation pathological phenomena, the patient maintaining her muscle tone through daily exercise using treadmill. Cardiological evaluation revealed no pathological elements and neurological examination was normal, the patient not showing any hearing changes at that moment. Bone Mineral Density (BMD) was measured via dual energy X-ray absorptiometry, and indicated a T score value of and a Z score f-2.6, indicating the presence of osteoporosis even under chronic treatment with antiresorptive medication from the age of 9 years. At the moment of presentation, the regimen for increasing the bone mineral density contained Ibandroic acid 150 mg / month, Alpha D 3 0.5μg / day and Coral D 1cp / day. Thoracic radiograph confirms the presence of moderate kyphoscoliosis, normal ribs and no post fractural changes (fig.2), pelvic radiograph captures bilateral coxa valga with cervical shaft angle of 160 degrees (fig. 3) and radiographs of the limbs identify deformities and osteoporosis in all skeletal parts (fig. 4). On the basis of the clinical and radiological changes captured, the patient has been included in the osteogenesis imperfecta type I. Fig. 2. Thoracic radiograph Fig. 3. Pelvic radiograph Fig. 4. Left femur deformation 159

4 D. Popescu et al. Laboratory tests being totally normal, it was opted for the surgical treatment of the fractured leg, which was implemented in the second day posttraumatic, under general anesthesia, spinal being a difficult choice in the context of existing changes in the lumbar spine. The tibial intramedullary canal extremely narrow and even disappeared in the distal portion, made intramedullary osteosynthesis impossible and an open reduction of the fracture by anterolateral approach and osteosynthesis with dynamic compression plate (DCP) placed on the lateral side of the distal tibia were practiced. The postoperative radiological control showed anatomical reduction of the fracture and correct positioning of the implant (fig. 5) Fig. 5. Postoperative result Postoperative evolution was favorable, it was applied a splint for 3 weeks, the partial support being resumed in 8 weeks postoperatively and the integral support in 12 weeks postoperatively, after radiological assessment confirmed the fracture healing (fig. 6) Clinical and radiological periodic reassessments have captured a favorable evolution with consolidation of the fracture, so that Fig. 6. Result after 12 weeks postoperative after 18 months postoperatively was chosen the ablation of the plate, followed by avoiding any support for 4 weeks. The patient returned to our service following a minor injury occurred 3 months after the removal of the plate, when she was diagnosed with an iterative fracture in the right leg and the therapeutic approach was represented by the resuming the osteosynthesis with DCP plate and healing of the bone (fig. 7). Fig. 7. Iterative fracture of the right leg and osteosyntesis with DCP plate 160

5 The risk of iterative fractures in patients with osteogenesis imperfecta - case report DISCUSSION Osteogenesis imperfecta type I is the mildest clinical expression of this disease and fortunately has the maximum prevalence. In most cases, this version has family history and autosomal dominant mode of transmission, but the possibility of this form of the disease to be a consequence of a de novo genetic mutation has also been demonstrated. In the mild forms of the disease, the fragility of bone system and joints hyperlaxity are due to an insufficient amount of collagen and the number of fractures in patients who have the mutation is 15 times higher compared with healthy children, existing the risk of being confused with a parental abuse (8). Exceeding the period of puberty makes the fractures frequency decrease. The longevity of these patients is not directly influenced by genetic mutation, but recurrent fractures and their complications can alter life expectancy. Serious forms that occur when collagen is not only insufficient, but also nonfunctional, can be diagnosed prenatally by specialized monitoring of risk pregnancies and fetal's DNA-analysis. Regarding the case presented with osteogenesis imperfecta type I, the patient has a consistent family history and the transmission was autosomal dominant. If one parent is affected by this genetic mutation, each child has a 50% chance to be born with this disease but the clinical expression may be totally different from that of their parents (9). The diagnosis was a clinical one and was suspected initially because of the modified color of sclera, later confirmed with the appearance of early fractures (starting from one year), of joints and skin hyperlaxity and bone deformities. No complex investigations such as quantitative and qualitative analysis of type I procollagen molecules obtained by biopsies from cultured skin fibroblasts or identification of genetic mutations in the blood cells DNA were conducted. According to studies, false negative results are obtained in 13.6% of cases. In the present case, the patient had multiple fractures, occurred starting with one year of age and produced by minor trauma. Administration of calcium preparations during childhood had not the desired favorable effect and the frequency of fractures decreased only after overcoming puberty. Clinical examination reveals the existence of a triangular face, blue sclera, joints hypermobility and no hearing damage. Radiological investigations confirm the presence of osteoporosis in all skeletal parts, including the spine, where was an evidence of a moderate scoliosis caused by unequal legs. The patient reported no history of rib fractures and thoracic radiographs confirmed the normal appearance of the ribs. The actual therapeutically management makes possible to achieve a quality of life close to normal, addressing osteogenesis imperfecta type I in multidisciplinary team: antiresorptive medication administration (bisphosphonates orally and intravenously) under the supervision of the endocrinologist, correction of deformities and treatment of fractures by orthopedic surgery, physiotherapist and physician s intervention of recovery to preserve joint mobility and maximizing physical performance. Bisphosphonate therapy was administered with caution in children at first, because it was considered a risk to disrupt the processes of mineralization and bone growth, emphasizing such deformities. Research published by Bianchi ML showed that administration of alendronate to children affected by osteogenesis imperfecta does not interfere with normal bone growth (10). 161

6 D. Popescu et al. CONCLUSIONS Our case is very suggestive for osteogenesis imperfecta type I, starting from the rich family history and especially the clinical manifestations and radiological evaluations. Insufficient amount of type I collagen is responsible for the existence of bone fragility and increased risk of fractures fallowing minimal trauma. Antiresorptive bisphosphonate therapy is effective for increasing bone strength, DNA tests conducted in patients who stopped the medication period indicate decreased bone mineral density. Stabilization of fractures in these patients is difficult due to the poor quality of bone tissue and to the atypical form of the skeletal parts because the long bones of patients are thin for their length and body weight and this condition tend to be more severe with age (11). Osteosynthesis with plates and screw provides a low resistance because of the failure of each screw and because of the stress riser effect at the plate ends (12). Although the centromedullar implant would have represented the ideal solution for stabilizing a fracture occurred on a bone with little resistance, we had to use plates that we could adapt intraoperatively to the tibial shape, because the small size and conformation of tibial canal did not allow the placement of a nail. Even if the radiological image showed normal aspect of consolidation and tibial cortices, removal of osteosynthesis material 18 months after implantation favored the reappearance of fracture in the old fracture place, with its recurrence 3 months after the ablation of the plate. Multidisciplinary approach of the patient with osteogenesis imperfecta significantly improves patient s quality of life. 162 REFERENCES 1. Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 1979; 16: Morgan JA, Marcus PS. Prenatal diagnosis and management of intrauterine fracture. Obstet Gynecol Surv 2010; 65(4): Marini JC. Osteogenesis imperfect. In: Behrman editor. Nelson's Textbook of Pediatrics. Atlanta: Elsevier, 1999, Martin E, Shapiro JR. Osteogenesis Imperfecta: epidemiology and pathophysiology. Curr Osteoporos Rep 2007; 5(3): Persiani P, Ranaldi FM, Martini L, Zambrano A, Celli M, D Eufemia P, Villani C. Osteogenesis imperfecta and clubfoot-a rare combination. Case report and review of the literature. Medicine 2016; 95: Glourieux FH. Osteogenesis Imperfecta. Best Pract Res Clin Rheumatol 2008; 22(1): Raunch F, Glourieux F.H. Osteogenesis Imperfecta, current and future medical treatment. Am J Med Genet C Semin Med Genet 2005; 139(91): Kocher MS, Kasser JR. Orthopaedic aspects of child abuse. J Am Acad Orthop Surg 2008; 8(1): Kukurila K, Grenman R, Johansson R, Kaitila I. Hearing loss in children osteogenesis imperfecta. Eur. J. Pediatr 2000; 259(7): Bianchi ML, Cimaz R et al. Efficacy and safety of alendronate for the treatment of osteoporosis in diffuse connective tissue diseases in children. Clin Pediatr (Phila) 2002; 41(5): Cho TJ, Lee K, Oh C, Park MS, MD, Yoo WJ, Choi IH. Locking Plate Placement with Unicortical Screw Fixation Adjunctive to Intramedullary Rodding in Long Bones of Patients with Osteogenesis Imperfecta. J Bone Joint Surg Am 2015; 97: Puvanesarajah V, Shapiro JR, Sponseller PD. Sandwich Allografts for Long-Bone Non-unions in Patients with Osteogenesis Imperfecta -A Retrospective Study. J Bone Joint Surg Am 2015; 97: