Underlying systemic mastocytosis in patients with unexplained osteoporosis: score proposal.

BACKGROUND: A score to predict the association between unexplained osteoporosis and an underlying systemic Mastocytosis (SM) is lacking. OBJECTIVE: This study aimed at identifying criteria able to predict the diagnosis of SM without skin involvement and provide an indication for bone marrow (BM) assessment. METHODS: We included 139 adult patients with unexplained osteoporosis and suspected SM. After BM evaluation, 63 patients (45.3 %) were diagnosed with SM, while the remaining 76 patients (54.7 %) negative for clonal mast cell (MC) disorders, constituted our control group. Univariate and multivariate analysis identified three independent predictive factors: age (<54 years: +1 point, >64 years: -1 point), serum basal tryptase (sBT) levels >19 ng/mL (+2 points) and vertebral fractures (+2 points). RESULTS: These variables were used to build the OSTEO-score, able to predict the diagnosis of SM before BM assessment with a sensitivity of 73.5 % and a specificity of 67.1 %. Patients with a score < 3 had a lower probability of having SM compared to patients with a score ≥ 3 (28.5 % and 71.4 %, respectively, p < 0.0001). When sBT levels were corrected for the presence of hereditary alpha-tryptasemia (HαT) using the BST calculater (https://bst-calculater.niaid.nih.gov/) recently published [1,2], the sensitivity of ΗαT-adjusted OSTEO-score increased to 87.8 %, and the specificity reached 76.1 %. Also, the positive predictive value of a score ≥ 3 increased to 85.2 %. CONCLUSIONS: Further studies are needed to validate these results and characterize the role of tryptase genotyping in patients with unexplained osteoporosis in reducing the risk of misdiagnosing patients with SM. Our proposed scoring model allows the identification of patients with the highest probability of having SM, avoiding unnecessary BM studies.

Surgical Strategies for Tuberculous Spondylodiscitis With Severe Osteoporosis: A Case Illustrating the Challenges of Delayed Intervention.

Tuberculous spondylodiscitis (Pott's spine) is a complex extrapulmonary manifestation of tuberculosis (TB) that poses significant medical challenges, characterized by vertebral destruction affecting approximately 2% of all TB cases. The management of this condition involves a multidisciplinary approach, with surgical intervention indicated for specific cases, including those with neurological complications, spinal instability, and kyphosis. We report a case of a 49-year-old female with a confirmed diagnosis of tuberculous spondylodiscitis who had undergone eight months of tuberculostatic therapy. She was referred for neurosurgical consultation due to uncontrollable axial pain, despite favorable clinical and imaging responses, which had rendered her immobile for six months. Imaging revealed a complete collapse of the L5 vertebral body, and a complementary dual x-ray absorptiometry (DEXA) scan demonstrated severe osteoporosis. A two-stage surgical approach was chosen to address her condition, involving corpectomy through an anterior approach, followed by lumbopelvic stabilization. Postoperative recovery was uneventful, with progressive improvement in pain and mobility. This case highlights the challenges of managing tuberculous spondylodiscitis and underscores the significance of early detection to prevent complications like severe osteoporosis. In this case, delayed referral for surgery following an extended period of immobility added complexity to an already difficult case. The severe osteoporosis, with a t-score of -5.7, had a substantial impact on surgical planning, leading to a more robust approach to arthrodesis with substantial lumbopelvic instrumentation in order to mitigate the risks associated with implant failure. This case shows that timely intervention and a comprehensive multidisciplinary approach are essential for the effective management of tuberculous spondylodiscitis, especially in cases complicated by severe osteoporosis.

The successful treatment of a Gustilo-Anderson type IIIc distal leg injury with a large bone defect in elderly patient with severe osteoporosis: a case report.

BACKGROUND: Gustilo-Anderson type IIIc tibial open fracture with large bone defects in elderly patients with severe osteoporosis is a rare injury that may be a challenging clinical scenario. CASE PRESENTATION: This study presents the case of a 68-year-old Japanese man who sustained a Gustilo-Anderson type IIIc open tibial fracture with a large bone defect. The patient had severe osteoporosis and the bone was contaminated; therefore, we determined that the bone could not be returned to the tibia. The patient underwent acute limb shortening and gradual lengthening with an Ilizarov external fixator combined with low-intensity pulsed ultrasound and teriparatide administration for limb reconstruction, which allowed immediate full weight-bearing capacity. The fixator was removed at 12 months postoperatively, and by this time, the fracture had completely healed. At the most recent 5-year follow-up after the injury, the patient reported full weight-bearing capacity without walking aids and had full knee and ankle range of motion. CONCLUSIONS: To the best of our knowledge, this is the first study to report the use of combined Ilizarov technique, low-intensity pulsed ultrasound, and teriparatide for limb reconstruction of Gustilo-Anderson type IIIc open tibial fractures with large bone defects in elderly patients with severe osteoporosis.

Efficacy of switching from teriparatide to zoledronic acid or denosumab on bone mineral density and biochemical markers of bone turnover in older patients with severe osteoporosis: a real-life study.

PURPOSE: Osteoporosis is characterized by loss of bone mass and susceptibility to fracture. Skeletal effects of teriparatide (TPT) are not persistent after drug withdrawal and sequential therapy with bisphosphonates or denosumab (Dmab) after TPT discontinuation represents a valid option. Here, the two sequential strategies were evaluated in severe osteoporotic patients. METHODS: The study retrospectively enrolled 56 severe osteoporotic patients who received TPT for 24 months followed by 24 months of zoledronic acid (ZOL) (TPT + ZOL) or Dmab (TPT+Dmab). Clinical features, incident fractures, bone mineral density (BMD) measurements, and bone marker profiles were collected. One-way ANOVA analyzed the difference between mean T-scores at baseline, after 24 months of TPT, and after 2 doses of ZOL or after at least 3 doses of Dmab. RESULTS: Twenty-three patients received TPT + ZOL (19 females, 4 males; median [IR] age, 74.3 [66.9, 78.6] years) and 33 patients received TPT+Dmab (31 females, 2 males; mean [IR] age, 66.6 ± 11.3 years). Mean lumbar and hip T-scores were increased after both TPT + ZOL and TPT+Dmab (all p < 0.05 vs baseline). The size effects induced by TPT + ZOL on the lumbar and hip BMD T-scores were similar to those observed with TPT+Dmab with mean T-scores increases of about 1 and 0.4 SD, respectively. No significant between-group differences were identified. Incident fragility fractures occurred in 3 (13%) patients treated with TPT + ZOL and in 5 (15%) patients treated with TPT+Dmab. CONCLUSIONS: Sequential TPT + ZOL therapy is likely to increase bone mineralization at the lumbar level and to stabilize it at the femoral level, similarly to what obtained with the sequential TPT+Dmab. Both ZOL and Dmab are suggested to be effective sequential treatments after TPT.

Osteoporosis related to WNT1 variants: a not infrequent cause of osteoporosis.

Nearly 10% of subjects with severe idiopathic osteoporosis present pathogenic WNT1 mutations. Clinical characteristics include a family history of osteoporosis, early adulthood onset, and fragility fractures which may evolve to pseudoarthrosis. WNT1 should be genetically screened in these patients as the phenotype is often variable and therapeutic approaches may differ. INTRODUCTION: Recent studies have shown that homozygous WNT1 gene mutations may be related to severe osteoporosis resembling osteogenesis imperfecta (OI). Conversely, heterozygous WNT1 mutations are linked to a milder phenotype of early-onset osteoporosis. Treatment with bisphosphonates is reported to be unsatisfactory. Our aim was to analyze the presence and prevalence of WNT1 mutations and the main associated clinical characteristics in subjects with primary early-onset osteoporosis. METHODS: A cohort comprising 56 subjects (aged 19-60 years) with severe, early-onset osteoporosis was screened by massive parallel sequencing with a 23-gene panel. The gene panel included 19 genes known to cause OI (including the WNT1 gene), three genes related to osteoporosis, and the gene related to hypophosphatasia (ALPL). RESULTS: We identified five patients (3 men) with heterozygous WNT1 variants. All presented severe osteoporosis with early fracture onset and a family history of fragility fractures. None presented a characteristic phenotype of OI or skeletal deformities. One patient was previously treated with bisphosphonates, presenting inadequate response to treatment and two developed pseudoarthrosis after upper arm fractures. All subjects were diagnosed in adulthood. CONCLUSIONS: Nearly 1/10 adult subjects with severe idiopathic osteoporosis may present pathogenic WNT1 mutations. Clinical characteristics commonly include a family history of osteoporosis, onset in early adulthood, marked decrease in bone mass, and prevalent fractures, particularly vertebral. WNT1 should be genetically screened in these subjects as the phenotype is often variable and the therapeutic approach may differ. The role of WNT1 mutations in the development of pseudoarthrosis should also be elucidated.

Alterations in the composition of the gut microbiota affect absorption of cholecalciferol in severe osteoporosis.

INTRODUCTION: To evaluate the relationship between the gut microbial composition and intestinal cholecalciferol absorption in patients with severe osteoporosis (SOP). MATERIALS AND METHODS: Eighteen patients with primary osteoporosis (OP) and 18 with SOP were included. Their clinical data were collected and their circulating concentrations of cholecalciferol and 25(OH)D3 were measured. Fecal samples were collected and their microbial contents were analyzed using 16S rDNA sequencing. RESULTS: The age, sex, body mass index, and body mass of the participants did not differ between the groups. The prevalence of gastrointestinal symptoms in the participants with SOP was significantly higher than that in the participants with OP. There were significant differences in the 25(OH)D3 and cholecalciferol concentrations between participants with SOP or OP and there was a significant positive correlation between the concentrations of these substance. The diversity of the gut microbiota in participants with SOP was significantly higher than that in participants with OP. Firmicutes was more abundant in the SOP group and the ratio of Firmicutes/Bacteroidetes in participants with SOP was higher. Conversely, Bifidobacterium was significantly less abundant, as were the order and family it belongs to. At the species level, Bifidobacterium was the most significant difference between the two groups. CONCLUSION: Differences in the intestinal microecology, especially Bifidobacterium, are associated with differences in the absorption of cholecalciferol and in the circulating 25(OH)D3 concentration, which may influence the progression of OP to SOP.

Internal medicine inpatients' prevalence of misdiagnosed severe osteoporosis.

Vertebral fractures (VF) related to osteoporosis (i.e., severe OP) increase the risk of disability and mortality, but they are often neglected. We observed a severe OP misdiagnosis in 28.9% of inpatients with previous spinal imaging positive for VFs. Diagnosing severe OP is crucial to reduce the health care costs of inpatients. INTRODUCTION: Vertebral fractures (VFs) related to osteoporosis (OP) increase the risk of additional fractures and death. In inpatients, VFs are often neglected with consequent delay in OP treatments, prolongation of hospitalization, and reduction of life expectancy. The aim of this study was to evaluate the prevalence of a misdiagnosed severe OP (i.e., with VF) in general medicine inpatients. METHODS: We evaluated inpatients of a Medicine Unit between January 2019 and December 2019 without severe OP diagnosis, who had spinal imaging. For each patient, we collected demographic data, previous or current OP treatment, and presence/number of VFs. Descriptive data were presented by medians (interquartile range [IQR]) for continuous data or as numbers (percentages) for categorical data. Differences between subgroups were analyzed with chi-square or Kruskal-Wallis tests as appropriate. p-values <0.05 were considered statistically significant. RESULTS: 793 subjects were admitted to inpatient's clinic: 235 (135 females and 100 males with a median age of 76.0 [64.0-83.0] years) were enrolled. One or more vertebral fractures were present in 28.9% (68/235) subjects; 47% (32/68) had two or more vertebral fractures. The majority of patients (55/68) with VFs had not previously received a severe OP diagnosis. CONCLUSIONS: Severe OP was misdiagnosed in at least 8.6% of inpatients. The prevalence dramatically increases (about 29%) in subjects with previous spinal imaging showing one or more VFs. More attention should be given to this co-morbidity, which is known to be an additional risk factor for disability and mortality.

Osteoporosis severa: fundamentos para su terapia farmacológica en México / Severe osteoporosis: Principles for pharmacological therapy in Mexico

Antecedentes: El presente artículo muestra la evidencia y recomendaciones de la eficacia y seguridad de las terapias hasta hoy aprobadas y disponibles en México para el tratamiento de la osteoporosis en su etapa severa o establecida, con la finalidad de establecer una postura terapéutica acerca de la eficacia y seguridad para esta etapa del padecimiento, de acuerdo con las cédulas descriptivas del Cuadro Básico y Catálogo de Medicamentos del Sector Salud en México. Métodos: Se realizó una revisión sistemática y narrativa de la evidencia de teriparatida y denosumab, desde su perfil farmacológico, efectividad y seguridad derivado de ensayos clínicos, además de un análisis de las recomendaciones generales de las principales guías de práctica clínica nacionales e internacionales. Resultados: La evidencia establece que teriparatida y denosumab pertenecen a clases terapéuticas distintas, con mecanismos de acción biológicamente opuestos e indicaciones de uso claramente diferenciadas en sus respectivas cédulas, por lo cual no son sustituibles ni intercambiables en la terapia de osteoporosis severa. Ambas representan la mejor opción disponible hasta el momento para esta etapa del padecimiento. Son similares en su eficacia de prevención de nuevas fracturas vertebrales por fragilidad, con un RR de 0,35 (IC 95%: 0,22-0,55) para teriparatida, y de 0,32 (IC 95%: 0,26-0,41) para denosumab. La reducción absoluta del riesgo es mayor con teriparatida 9,3% (21 meses) que con denosumab 4,8% (36 meses). Conclusiones: Nuestros resultados concuerdan con las recomendaciones disponibles en las principales guías de práctica clínica nacionales e internacionales, por lo que son propuestas ambas terapias como consecutivas y nunca como sustitutivas.(AU)

Background: This article presents evidence and recommendations regarding the efficacy and safety of the approved and available therapies in Mexico to treat severe or established osteoporosis with the aim of developing a position regarding therapeutics in this stage of the disease, according to the descriptive cards of the National Drug Formulary of the National General Health Council of Mexico. Methods: We performed a systematic and narrative review of the evidence of teriparatide and denosumab, from their pharmacological profile, effectiveness, and safety derived from clinical trials, as well as an analysis of the general recommendations of the national and international clinical practice guidelines. Results: The evidence establishes that teriparatide and denosumab belong to different therapeutic classes, with biologically opposed mechanisms of action and indications of use, which are clearly differentiated in their respective national codes, therefore these drugs cannot be substitutable or interchangeable in severe osteoporosis therapy. Both represent the best options currently available for this stage of the disease; being similar in their efficacy in preventing new vertebral fragility fractures, with an RR of .35 (CI 95%; .22-.55) for teriparatide, and .32 (CI 95%: .26-.41) for denosumab. The absolute risk reduction is higher with teriparatide 9.3% (21 months) compared with denosumab at 4.8% (36 months). Conclusions: Our results agree with the recommendations available in national and international clinical practice guidelines, with both therapies proposed as a sequential, but not a substitute, treatment.(AU)

Severe osteoporosis: Principles for pharmacological therapy in Mexico. / Osteoporosis severa: fundamentos para su terapia farmacológica en México.

BACKGROUND: This article presents evidence and recommendations regarding the efficacy and safety of the approved and available therapies in Mexico to treat severe or established osteoporosis with the aim of developing a position regarding therapeutics in this stage of the disease, according to the descriptive cards of the National Drug Formulary of the National General Health Council of Mexico. METHODS: We performed a systematic and narrative review of the evidence of teriparatide and denosumab, from their pharmacological profile, effectiveness, and safety derived from clinical trials, as well as an analysis of the general recommendations of the national and international clinical practice guidelines. RESULTS: The evidence establishes that teriparatide and denosumab belong to different therapeutic classes, with biologically opposed mechanisms of action and indications of use, which are clearly differentiated in their respective national codes, therefore these drugs cannot be substitutable or interchangeable in severe osteoporosis therapy. Both represent the best options currently available for this stage of the disease; being similar in their efficacy in preventing new vertebral fragility fractures, with an RR of .35 (CI 95%; .22-.55) for teriparatide, and .32 (CI 95%: .26-.41) for denosumab. The absolute risk reduction is higher with teriparatide 9.3% (21 months) compared with denosumab at 4.8% (36 months). CONCLUSIONS: Our results agree with the recommendations available in national and international clinical practice guidelines, with both therapies proposed as a sequential, but not a substitute, treatment.

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.

Severe Idiopathic Osteoporosis in a Premenopausal Woman: A Case for Dual Therapy.

Currently available agents improve bone mineral density (BMD) values on their own in monotherapy but may not completely restore microarchitecture and the patient may continue to sustain fragility fractures. Current monotherapies can only address either increased bone resorption or decreased bone formation. In this setting, combination therapy with antiresorptive and anabolic agents appears to be a promising option. A 49-year-old premenopausal woman presented with severe low backache associated with significant height loss. Evaluation elsewhere revealed severe osteoporosis, which prompted treatment with three doses of parenteral zoledronate 4 mg annually, followed by oral alendronate 70 mg once weekly for 7 years. However, her symptoms persisted despite treatment, and investigations done at our center confirmed severe osteoporosis, with multiple vertebral compression fractures. She was initiated on teriparatide therapy but despite 1 year of treatment, there was persistent height loss. In addition, there was a marked elevation of bone resorption, which prompted us to add denosumab which was administered subcutaneously every 6 months. On follow-up, there was marked relief from pain, no further decrease in height, and progressive improvement in BMD, and bone turnover markers were noted. A dual therapy with anabolic agent teriparatide and antiresorptive agent denosumab for osteoporosis may be a viable option in individuals with severe osteoporosis who do not respond well to a single agent.

Papillary thyroid carcinoma is a risk factor for severe osteoporosis.

INTRODUCTION: Thyroid-stimulating hormone (TSH)-suppressive therapy is recommended after surgical treatment in high-risk papillary thyroid carcinoma (PTC) patients. TSH-suppressive therapy is a known risk factor for osteoporosis and fractures. However, whether patients with PTC themselves are at a higher risk of osteoporosis than healthy individuals remains unclear. This study aimed to clarify whether PTC is a risk factor for osteoporosis. MATERIALS AND METHODS: Serum and urinary biochemical parameters, bone mineral density (BMD), and presence of vertebral fractures (VFs) and non-VFs were evaluated in 35 PTC patients and 35 age- and sex-matched healthy individuals. We compared the parameters between PTC and control subjects and performed multiple logistic regression analyses after adjustments for variables. RESULTS: Patients with PTC had higher body mass index (BMI) and hemoglobin (Hb)A1c, as well as lower eGFR and intact PTH than controls (p < 0.05, each). There were no significant differences in the prevalence of osteoporosis and VFs and non-VFs between patients with PTC and controls. However, the prevalence of severe osteoporosis diagnosed according to WHO criteria was significantly higher in PTC subjects (34.3%) than in controls (11.4%, p < 0.05). Multivariate logistic regression analyses adjusted for age, BMI, eGFR and HbA1c identified PTC as being associated with the presence of severe osteoporosis (odds ratio, 4.20; 95% confidence interval, 1.05-16.8; p < 0.05). CONCLUSIONS: We identified PTC as a risk factor for severe osteoporosis, independent of BMI, renal function and glucose profile.

Retention of osteocytic micromorphology by sclerostin antibody in a concurrent ovariectomy and functional disuse model.

Prolonged mechanical unloading in bedridden patients and concurrent hormonal dysregulation represents the cause of one of the severest forms of osteoporosis, a condition for which there are very few efficacious interventions available to date. Sclerostin, a Wnt antagonist, acts as a negative regulator of bone formation. Sclerostin antibody (Scl-Ab)-mediated blockade of sclerostin can dramatically enhance bone formation and reduce bone resorption. This study was designed to investigate the therapeutic effect of the Scl-Ab on severe bone loss induced by concurrent mechanical unloading and estrogen deficiency in a hindlimb-suspended and ovariectomized rat model, and to study the cellular mechanisms underlying severe osteoporosis and Scl-Ab action. Unloading and ovariectomy resulted in severe loss of trabecular and cortical bone mass and strength; Scl-Ab can significantly counteract the deterioration of bone in unloaded and/or ovariectomized rats, with noticeably increased cortical bone formation. Scanning electron microscopy analysis revealed that unloading and ovariectomy lead to multiple morphological and structural abnormalities of osteocytes in cortical bone and the abnormalities were abolished by Scl-Ab administration. This study extends our previous conclusion that Scl-Ab represents a promising therapeutic approach for severe bone loss that occurs after being exposed to estrogen deficiency and prolonged mechanical unloading.

Biomechanical study of injectable hollow pedicle screws for PMMA augmentation in severely osteoporotic lumbar vertebrae: effect of PMMA distribution and volume on screw stability.

OBJECTIVEThe purpose of this study was to compare stability of injectable hollow pedicle screws with different numbers of holes using different volumes of polymethylmethacrylate (PMMA) in severely osteoporotic lumbar vertebrae and analyze the relationship between screw stability and distribution and volume of PMMA.METHODSForty-eight severely osteoporotic cadaveric lumbar vertebrae were randomly divided into 3 groups-groups A, B, and C (16 vertebrae per group). The screws used in group A had 4 holes (2 pairs of holes, with the second hole of each pair placed 180° further along the thread than the first). The screws used in group B had 6 holes (3 pairs of holes, placed with the same 180° difference in position). Unmodified conventional screws were used in group C. Each group was randomly divided into subgroups 0, 1, 2, and 3, with different volumes of PMMA used in each subgroup. Type A and B pedicle screws were directly inserted into the vertebrae in groups A and B, respectively, and then different volumes of PMMA were injected through the screws into the vertebrae in subgroups 0, 1, 2, and 3. The pilot hole was filled with different volumes of PMMA followed by insertion of screws in groups C0, C1, C2, and C3. Distributions of PMMA were evaluated radiographically, and axial pull-out tests were performed to measure the maximum axial pullout strength (Fmax).RESULTSRadiographic examination revealed that PMMA surrounded the anterior third of the screws in the vertebral bodies (VBs) in groups A1, A2, and A3; the middle third of screws in the junction area of the vertebral body (VB) and pedicle in groups B1, B2, and B3; and the full length of screws evenly in both VB and pedicle in groups C1, C2, and C3. In addition, in groups A3 and B3, PMMA from each of the screws (left and right) was in contact with PMMA from the other screw and the PMMA was closer to the posterior wall and pedicle than in groups A1, A2, B1, and B2. One instance of PMMA leakage was found (in group B3). Two-way analysis of variance revealed that 2 factors-distribution and volume of PMMA-significantly influenced Fmax (p < 0.05) but that they were not significantly correlated (p = 0.078). The Fmax values in groups in which screws were augmented with PMMA were significantly better than those in groups in which no PMMA was used (p < 0.05).CONCLUSIONSPMMA can significantly improve stability of different injectable pedicle screws in severely osteoporotic lumbar vertebrae, and screw stability is significantly correlated with distribution and volume of PMMA. The closer the PMMA is to the pedicle and the greater the quantity of injected PMMA used, the greater the pedicle screw stability is. Injection of 3.0 mL PMMA through screws with 4 holes (2 pair of holes, with the screws in each pair placed on opposite sides of the screw) produces optimal stability in severely osteoporotic lumbar vertebrae.

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.

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.

Staged Correction of Severe Thoracic Kyphosis in Patients with Multilevel Osteoporotic Vertebral Compression Fractures.

Study Design Technical report. Objective Multilevel osteoporotic vertebral compression fractures may lead to considerable thoracic deformity and sagittal imbalance, which may necessitate surgical intervention. Correction of advanced thoracic kyphosis in patients with severe osteoporosis remains challenging, with a high rate of failure. This study describes a surgical technique of staged vertebral augmentation with osteotomies for the treatment of advanced thoracic kyphosis in patients with osteoporotic multilevel vertebral compression fractures. Methods Five patients (average age 62 ± 6 years) with multilevel osteoporotic vertebral compression fractures and severe symptomatic thoracic kyphosis underwent staged vertebral augmentation and surgical correction of their sagittal deformity. Clinical and radiographic outcomes were assessed retrospectively at a mean postoperative follow-up of 34 months. Results Patients' self-reported back pain decreased from 7.2 ± 0.8 to 3.0 ± 0.7 (0 to 10 numerical scale; p < 0.001). Patients' back-related disability decreased from 60 ± 10% to 29 ± 10% (0 to 100% Oswestry Disability Index; p < 0.001). Thoracic kyphosis was corrected from 89 ± 5 degrees to 40 ± 4 degrees (p < 0.001), and the sagittal vertical axis was corrected from 112 ± 83 mm to 38 ± 23 mm (p = 0.058). One patient had cement leakage without subsequent neurologic deficit. Decreased blood pressure was observed in another patient during the cement injection. No correction loss, hardware failure, or neurologic deficiency was seen in the other patients. Conclusion The surgical technique described here, despite its complexity, may offer a safe and effective method for the treatment of advanced thoracic kyphosis in patients with osteoporotic multilevel vertebral compression fractures.

Sclerostin antibody prevented progressive bone loss in combined ovariectomized and concurrent functional disuse.

Osteoporosis is characterized by low bone mass and compromised trabecular architecture, and is commonly occurred in post-menopausal women with estrogen deficiency. In addition, prolonged mechanical unloading, i.e., long term bed rest, can exaggerate the bone loss. Sclerostin is a Wnt signaling antagonist and acts as a negative regulator for bone formation. A sclerostin-neutralizing antibody (Scl-Ab) increased bone mineral density in women with postmenopausal osteoporosis and healthy men. The objective of this study was to characterize the condition of bone loss in ovariectomized (OVX) rats with concurrent mechanical unloading and evaluate the effect of sclerostin antibody treatment in mitigating the prospective severe bone loss conditions in this model. Four-month-old OVX- or sham-operated female SD rats were used in this study. They were subjected to functional disuse induced by hind-limb suspension (HLS) or free ambulance after 2days of arrival. Subcutaneous injections with either vehicle or Scl-Ab at 25mg/kg were made twice per week for 5weeks from the time of HLS. µCT analyses demonstrated a significant decrease in distal metaphyseal trabecular architecture integrity with HLS, OVX and HLS+OVX (bone volume fraction decreased by 29%, 71% and 87% respectively). The significant improvements of various trabecular bone parameters (bone volume fraction increased by 111%, 229% and 297% respectively as compared with placebo group) with the administration of Scl-Ab are associated with stronger mechanical property and increased bone formation by histomorphometry. These results together indicate that Scl-Ab prevented the loss of trabecular bone mass and cortical bone strength in OVX rat model with concurrent mechanical unloading. The data suggested that monoclonal sclerostin-neutralizing antibody represents a promising therapeutic approach for severe osteoporosis induced by estrogen deficiency with concurrent mechanical unloading.

Vertebral fracture assessment by DXA is inferior to X-ray in clinical severe osteoporosis.

UNLABELLED: Spine fractures are diagnosed by X-ray or vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA) scanning. The use of VFA evaluation by DXA is still debated. We demonstrate that VFA is inferior relative to X-ray in visualizing vertebrae properly in the upper spine and therefore with a reduced diagnostic performance in detecting fractures. INTRODUCTION: Vertebral fracture assessment (VFA) by DXA has been evaluated for many years, and its use in clinical practice is still debated. In a cross-sectional setting, we aimed to compare VFA with traditional radiography in vertebral fracture (VF) diagnosis in severe osteoporotic patient. METHODS: A total of 207 patients referred to the outpatient clinic for teriparatide treatment were screened, out of whom 35 (16.9 %) severe osteoporotic patients were identified (mean age 67.5 ± 11.3 years and median T-score -3.2 interquartile range (IQR) (-1.9 to -3.7). VF diagnosis was performed independently using VFA and X-ray in accordance with the semiquantitative (SQ) approach. The same technician performed the primary interpretation on both sets of images, after which a radiologist and an endocrinologist reviewed the evaluation for a conclusive judgement. RESULTS: In total, 180 radiographic fractures were detected, corresponding to 5.1 fractures per individual. Using VFA, 18.5 % of vertebrae were considered unreadable, compared to 2.0 % on X-ray. The accuracy of VFA in VF detection using X-ray as a reference resulted in sensitivity and specificity of 75.5 and 86.7 %, respectively. Sensitivity decreased from the lumbar to thoracic level. Nevertheless, VFA only identified fractures consistently between Th11 and L3. CONCLUSION: Our data, based on a severe osteoporotic population, demonstrate that VFA is inferior relative to X-ray in visualizing vertebrae properly in the upper spine, resulting in vertebrae not being assessable for analysis and a reduced diagnostic performance in detecting fractures. Improvements in DXA techniques are needed for it to be comparable with X-ray in VF diagnosis.