Osteoporosis grave secundaria a enfermedad de Gaucher: reporte de caso / Severe osteoporosis secondary to Gaucher disease: case report

La enfermedad de Gaucher (EG) es un trastorno genético lisosomal autosómico recesivo infrecuente, que conduce a la acumulación de lípidos y disfunción en múltiples órganos. La afectación del esqueleto es uno de los hallazgos más frecuentes de la EG y una de las principales causas de dolor y reducción de calidad de vida. El compromiso esquelético incluye anomalías en el remodelado óseo con pérdida mineral ósea, adelgazamiento cortical, lesiones líticas, fracturas por fragilidad y deformidades articulares. A continuación presentamos el caso de una paciente 61 años con osteoporosis grave secundaria a EG diagnosticada en la vida adulta, con antecedente de dos hermanas con EG. La paciente refería dolores óseos y lumbago crónico desde los 53 años. El 2012 fue evaluada en policlínico de hematología por trombocitopenia y debido a sus antecedentes familiares se le solicitaron exámenes que fueron compatibles con EG. El año 2016 la densitometría ósea (DXA) de columna lumbar y cuello femoral izquierdo, que mostró una osteoporosis. Se inició tratamiento con Alendronato, Calcio y Vitamina D, pero la paciente tuvo escasa adherencia. El 2018 se inició tratamiento de su EG con Taliglucerasa α. Al año siguiente se le realizó nueva DXA que evidenció persistencia de la osteoporosis y por mantención del lumbago se le solicitó una TAC de columna lumbar que mostró fracturas por aplastamiento de cuerpos vertebrales dorsales bajos. Se derivó a endocrinología para manejo de su osteoporosis grave. A su ingreso a endocrinología la paciente persitía con dolor lumbar alto y destacaba una marcada cifosis. Se decidió retomar tratamiento con Alendronato, calcio y vitamina D, además, se le solicitó una nueva evaluación densitométrica junto a una radiografía de columna total y evaluación dental. Durante el seguimiento la paciente mantuvo niveles de vitamina D adecuados con funciones renal, hepática y tiroidea normales.

Gaucher disease (GD) is a rare autosomal recessive lysosomal genetic disorder, leading to the accumulation and dysfunction of lipids in multiple organs. Skeletal involvement is one of the most prevalent aspects of GD and one of the main causes of pain and reduced quality of life. Abnormalities of bones, which cause changes in the development and loss of bone mineral, cortical thinning, lytic lesions,fragility fractures and deformities. We present a case of a patient diagnosed with severe osteoporosis, secondary to GD diagnosed in adult life. The patient presents a disease pattern composed of bone pain and chronic low back pain since the age of 53. In 2012, she was evaluated at the hematology for thrombocytopenia and due to her family history, tests were performed to diagnose GD, which were compatible with it. In 2016 Bone Densitometry (DXA) of the lumbar spine and left femoral neck was requested, being consistent with osteoporosis. Treatment with Alendronate, Calcium and Vitamin D was started, however, there is little adherence. In 2018, treatment for Gaucher's disease was started with Taliglucerase α. The following year, DXA was performed with few changes and a CT scan of the lumbar spine was performed diagnosing crush fractures of the low dorsal vertebral bodies. She was referred to endocrinology. Upon admission to Endocrinology, it was decided to resume initial osteoporosis treatment and to perform skeletal evaluation with DXA of the lumbar spine and hips, total spine X-ray and dental evaluation. During follow-up, it maintains vitamin D at adequate levels and normal kidney, liver and thyroid functions.

Surgical treatment of severe osteoporosis including new concept of advanced severe osteoporosis

Severe osteoporosis is classified as those with a bone mineral density (BMD) T-score of −2.5 or lower, and demonstrate one or more of osteoporotic, low-trauma, fragility fractures. According to the general principle of surgical approach, patients with severe osteoporosis require not only more thorough pre- and postoperative treatment plans, but improvements in surgical fixtures and techniques such as the concept of a locking plate to prevent bone deformity and maximizing the blood flow to the fracture site by using a minimally invasive plate osteosynthesis. Arthroplasty is often performed in cases of displaced femoral neck fracture. Otherwise internal fixation for the goal of bone union is the generally accepted option for intertrochanteric, subtrochanteric, and femoral shaft fractures. Most of osteoporotic spine fracture is stable compression fracture, but vertebroplasty or kyphoplasty may be performed some selective patients. If neurological paralysis, severe spinal instability, or kyphotic deformity occurs, open decompression or fusion surgery may be considered. In order to overcome shortcomings of the World Health Organization definition of osteoporosis, we proposed a concept of ‘advanced severe osteoporosis,’ which is defined by the presence of proximal femur fragility fracture or two or more fragility fractures in addition to BMD T-score of −2.5 or less. In conclusion, we need more meticulous approach for surgical treatment of severe osteoporosis who had fragility fracture. In cases of advanced severe osteoporosis, we recommend more aggressive managements using parathyroid hormone and receptor activator of nuclear factor kappa-B ligand monoclonal antibody.

Medical treatment of severe osteoporosis including new concept of advanced severe osteoporosis

Osteoporosis is a metabolic bone disease characterized by decreased bone strength, leading to an increased risk of fracture. The World Health Organization (WHO) defines osteoporosis as a bone mineral density (BMD) of 2.5 standard deviations below that of a young adults (T-score of -2.5 or lower). Severe osteoporosis is differentiated from osteoporosis by the presence of one or more fragility fractures in addition to this T-score. However, the current WHO definition may be insufficient to reflect the diverse spectrum of osteoporosis or severe osteoporosis, which can encompass various number and severity of prevalent fractures. To overcome these shortcomings of the WHO definition of osteoporosis, we propose a concept of 'advanced severe osteoporosis', which is defined by the presence of proximal femur fragility fracture or two or more fragility fractures in addition to BMD T-score of -2.5 or less. Based on the previous clinical trials and post-hoc analyses, we recommend selective estrogen receptor modulators, bisphosphonates, receptor activator of nuclear factor kappa-B ligand (RANKL) monoclonal antibody, and parathyroid hormone for the medical treatment of severe osteoporosis. In cases of advanced severe osteoporosis or osteoporosis that does not respond to previous anti-osteoporotic treatments, we also recommend parathyroid hormone, bisphosphonates, and RANKL monoclonal antibody. In conclusion, we need more precise assessment of osteoporosis and further stratification of the disease by number of prevalent fractures in addition to BMD. More aggressive managements should be provided for those with advanced severe osteoporosis.

Severe Osteoporosis and Advanced Severe Osteoporosis / 대한골다공증학회지

The definition of severe or established osteoporosis was identified as the reduced bone density, with a T-score value below the

Tratamiento de la osteoporosis grave con teriparatide / Severe osteoporosis treatment with teriparatide

El objetivo de este trabajo retrospectivo fue evaluar el tratamiento de la osteoporosis grave con teriparatide (PTH) y comparar nuestros resultados con los publicados en la literatura médica. Se incluyeron cuarenta y seis pacientes, cuarenta y dos mujeres y cuatro varones, edad: 69.15 ± 9.43 años. Seis eran vírgenes de tratamiento y cuarenta tratados previamente con bisfosfonatos. Treinta y dos pacientes habían tenido 93 fracturas de las cuales 86 vertebrales. Cuarenta y seis recibieron PTH 6 meses, 29 pacientes durante 12 meses y 20 completaron los 18 meses sugeridos. La densidad mineral ósea (DMO) de columna lumbar aumentó significativamente desde el primer control a los 6 meses (p < 0.0001). La DMO de cuello de fémur alcanzó un incremento significativo al final del tratamiento (p = 0.002). La osteocalcina aumentó significativamente al mes, seguido por el ß crosslaps (beta-CTx, prueba en suero) al tercer mes y la fosfatasa alcalina ósea, regresando los marcadores de recambio óseo a niveles basales a los 18 meses. Las calcemias y las calciurias no se modificaron significativamente, pero 8 pacientes tuvieron hipercalcemias leves y tres hipercalciurias asintomáticas. El tratamiento fue bien tolerado y no se registraron efectos adversos graves que requirieran suspender el tratamiento. En conclusión, la PTH es una alternativa útil y segura para el tratamiento de la osteoporosis grave. Nuestros resultados concuerdan con los previamente publicados en la literatura médica.

The primary objective of this retrospective study was to evaluate the treatment of severe osteoporosis with teriparatide (PTH) and to compare our results with those published in the literature. We included 46 patients, 42 women and four men, mean age: 69.15 ± 9.43 years. Six patients were treatment naive and forty previously treated with bisphosphonates. Thirty-two patients had had 93 fractures of which 86 vertebral. Forty-six received PTH for 6 months, twenty-nine for 12 months and twenty completed the 18 months suggested. Bone mineral density (BMD) of the lumbar spine increased significantly at the first control performed at six months of treatment (p < 0.0001), and the femoral neck BMD reached a significant increase at the end of treatment (p = 0.002). Serum osteocalcin values significantly increased from the first month of treatment, followed by ß crosslaps (beta-CTx, serum test) and bone-specific alkaline phosphatase, returning all the markers of bone turnover to baseline levels at 18 months. Serum and urinary calcium did not change significantly at any time, but 8 (17.9%) patients developed mild hypercalcemia and 3 (6.5%) asymptomatic hypercalciuria. The treatment was well tolerated and there were no serious adverse events requiring discontinuation. In conclusion, PTH is a safe and useful alternative for the treatment of primary severe osteoporosis. Our results agree with those previously reported in the literature.

Clinical Efficacy of Bone Cement Augmented Screw Fixation for the Severe Osteoporotic Spine

OBJECTIVE: Transpedicular instrumentation of the osteoporotic spine is a challenge for the spine surgeon due to the probability of screw loosening and the potential possibility of nonunion. The purpose of this study was to evaluate the clinical efficacy of bone cement augmented screw fixation in patients with severe osteoporosis. METHODS: Between February 2004 and August 2007, 250 patients with severe osteoporosis (T-score on BMD < -3.0) that had screw fixation were included in this study. The patients were divided into two groups (Group I: 157 patients that underwent bone cement augmented screw fixation that had a variety of spine spinal diseases including fractures, and Group II: 93 patients with severe osteoporosis that had screw fixation without bone cement augmentation). The imaging and clinical features were analyzed, including bone cement augmented levels, fusion rate and related complications. The visual analog scale (VAS), Oswestry disability questionnaire (ODI) and modified MacNab's criteria were used for the assessment of pain and functional capacity. RESULTS: In both groups, a significant improvement in the VAS and ODI was achieved. 146 out of 157 patients (93%) in Group I and 83 out of 93 patients (90%) in Group II were graded as an excellent or good result according to the modified MacNab's criteria. None of the patients experienced serious complications. However, there were two cases with neurological deterioration as a result of bone cement extravasation in Group I. For Group II, there were five cases of screw loosening that required re-operation for bone cement augmentation. CONCLUSION: Whether bone cement augmentation was performed or not, it was possible to achieve satisfactory results in patients with severe osteoporosis. However, if used carefully, bone cement augmented transpedicular screwing can reduce screw loosening and pullout in patients with severe osteoporosis.

Clinical Efficacy of Bone Cement Augmented Screw Fixation for the Severe Osteoporotic Spine

OBJECTIVE: Transpedicular instrumentation of the osteoporotic spine is a challenge for the spine surgeon due to the probability of screw loosening and the potential possibility of nonunion. The purpose of this study was to evaluate the clinical efficacy of bone cement augmented screw fixation in patients with severe osteoporosis. METHODS: Between February 2004 and August 2007, 250 patients with severe osteoporosis (T-score on BMD < -3.0) that had screw fixation were included in this study. The patients were divided into two groups (Group I: 157 patients that underwent bone cement augmented screw fixation that had a variety of spine spinal diseases including fractures, and Group II: 93 patients with severe osteoporosis that had screw fixation without bone cement augmentation). The imaging and clinical features were analyzed, including bone cement augmented levels, fusion rate and related complications. The visual analog scale (VAS), Oswestry disability questionnaire (ODI) and modified MacNab's criteria were used for the assessment of pain and functional capacity. RESULTS: In both groups, a significant improvement in the VAS and ODI was achieved. 146 out of 157 patients (93%) in Group I and 83 out of 93 patients (90%) in Group II were graded as an excellent or good result according to the modified MacNab's criteria. None of the patients experienced serious complications. However, there were two cases with neurological deterioration as a result of bone cement extravasation in Group I. For Group II, there were five cases of screw loosening that required re-operation for bone cement augmentation. CONCLUSION: Whether bone cement augmentation was performed or not, it was possible to achieve satisfactory results in patients with severe osteoporosis. However, if used carefully, bone cement augmented transpedicular screwing can reduce screw loosening and pullout in patients with severe osteoporosis.

Bone Cement Augmented Screw Fixation for Severe Osteoporotic Spine: Large Series of Clinical Application

OBJECTIVE: The purpose of this study was to evaluate the clinical efficacy of bone cement augmented screw fixation for the patients accompanying severe osteoporosis. METHODS: Between February 2004 and August 2007, 157 patients with various spinal diseases including fractures accompanying severe osteoporosis underwent a bone cement augmented screw fixation (947 levels). About 4.8cc of polymethylmethacrylate was injected into the each vertebral body through transpedicular route. We divided the patients into two groups (Group I: Posterior fusion for compression/burst fractures or idiopathic scoliosis, Group II: Interbody fusion for various spinal diseases). Imaging and clinical features were analyzed, including bone cement augmented levels, fusion rate, clinical outcome and complications. The visual analog scale (VAS), Oswestry disability questionnaire and modified MacNab's criteria were used for the assessment of pain and functional capacity. RESULTS: In both groups, a significant improvement in VAS and Oswestry disability questionnaire was achieved. 146 out of 157 patients (93%) were graded as excellent or good result according to the modified MacNab's criteria. None of the patients experienced operative death, screw pullout or cut-up. However, there were two cases of neurologic deterioration as a result of bone cement extravasation. CONCLUSION: Bone cement augmented transpedicular screwing can reduce the possibility of screw loosening and pullout in patients with severe osteoporosis.

Bone Cement Augmentation of Pedicular Screwing in Severe Osteoporotic Spondylolisthetic Patients

OBJECTIVE: The purpose of this study was to determine the effect of bone cement augmentation of pedicular screwing in severe osteoporotic spondylolisthetic patients. METHODS: Twenty patients with spondylolisthesis (8 : spondylolytic spondylolisthesis 12 : degenerative spondylolisthesis) who had undergone pedicular screwing and interbody fusion for osteoporotic lumbar spine (T-score on bone mineral density<-3.0) from 2002 to 2005 were reviewed. Mean age was 62.3 years with 3 male and 17 female patients. Average follow-up period was 14 months. Average T-score on bone mineral density (BMD) was -3.62. After decompression of neural elements, about 6cc of polymethylmethacrylate (PMMA) was injected into the each vertebral body through transpedicular route. All patients underwent one level interbody fusion and pedicular screw fixation. Clinical outcome was assessed using Oswestry Disability Index (ODI) on the last clinical follow-up. In addition, a modified MacNab's grading criteria was used to objectively assess patient's outcome postoperatively. Radiographic analysis of sagittal contour was assessed preoperatively, immediately postoperatively, and at final follow-up including fusion rate. RESULTS: Eighteen of 20 patients were graded as excellent or good according to the modified MacNab's criteria. An significant improvement of ODI was achieved in both groups. Mean sagittal angle at the preoperative state, postoperative state and at the last follow-up state was 11.0 degrees, 20.1 degrees and 18.3 degrees, respectively, with mean sagittal angle correction gain 7.3 degrees. Firm fusion was achieved in all patients. There were one compression fracture above the fused segment after 6 months follow-up and one case of seroma. But, there were no postoperative complications related to bone cement leakage and pedicular screwings such as screw pullout or screw cut-up. CONCLUSION: Bone cement augmentation of pedicular screwing can be an effective procedure for osteoporotic lumbar spine in spondylolisthetic patients.

Long Term Result of Pediculectomy in Symptomatic Isthmic Spondylolisthesis with Severe Osteoporosis

OBJECTIVE: Patients with symptomatic root compression in isthmic spondylolisthesis are commonly treated by bilateral wide posterior decompression and concomitant fusion with transpedicular instrumentation. But, in cases associated with severe osteoporosis or poor general conditions for surgery, high fusion failure rate or high operation risk is expected. The authors report the results of partial pediculectomy for root decompression without fusion procedure in 7 cases. Followed up period was over 3 years. METHODS: From December 1993 to May 1998, we performed operation in 87 patients with isthmic spondylolesthesis. Posterior lumbar interbody fusion was performed in 80 cases. Unilateral or bilateral removal of about 3mm length of infero-medial part of pedicle was performed in six cases who were associated with severe osteoporosis(T < -3.0 , BMD) and in 1 case with high risk cardiac disease. RESULTS: Radiating pain disappeared immediately after the surgery in all cases. There were no increasing instability after surgery. In long-term follow up, aggravation of symptoms were observed in 3 cases. In one of these 3 patients(high risk cardiac disease patient) bilateral wide decompression and bone fusion with transpedicular screwing was performed. CONCLUSION: In the surgical treatment of osteoporotic isthmic spondylolisthesis with foraminal stenosis in which transpedicular screwing and fusion is not indicated, partial pediculectomy without stabilization may be a effective method for relieving radicular pain, but in part of these patients symptoms may recur in long-term follow up.