Vertebroplasty and kyphoplasty as treatment for osteoporotic vertebral fractures

Summary Over the last decade vertebroplasty and kyphoplasty have become popular as therapeutic options for the treatment of vertebral fractures. In fact, numerous non-controlled studies have indicated that both procedures are very efficacious for the control of pain associated with fractures. However, some recently published randomised trials have cast doubt on the true effectiveness of these procedures. On the other hand, certain observations have suggested that the increase in the rigidity which is produced by the injection of metacrylate into a vertebral body could facilitate the collapse of the adjacent vertebra. Therefore, vertebroplasty and kyphoplasty should not be considered as a routine theraputic measure, but should be limited to carefully selected patients, in whom the potential benefits surpass the risks and costs of the procedure. In any case, the patients should be put on a global treatment programme which includes pharmaceutical measures and non-pharmaceutical care to reduce the risk of future vertebral and peripheral fractures. Various clinical trials have recently been published which were supposed to be an important contribution to knowledge regarding the effectiveness of vertebroplasty. The results have been rather contradictory both within themselves, and with earlier observational studies. For this reason it is worth reviewing this questions with the intention of helping clinicians who need to take decisions on the treatment of patients with osteoporotic fractures. We have not dealt with the possible utility vertebroplasty in other processes, such as fractures caused by tumours or by trauma

Hypercalcemia in patients with rheumatoid arthritis: a retrospective study

Objetivo: Investigar la prevalencia de hipercalcemia en pacientes con artritis reumatoide (AR) y analizar las características clínicas y las causas de la hipercalcemia. Material y métodos: Estudio retrospectivo de revisión basado en casos que incluyó 500 pacientes con AR. Se identificaron los pacientes con niveles de calcio aumentados en al menos dos ocasiones. Resultados: La hipercalcemia estuvo presente en 24 de los 500 pacientes con AR (4,8%). La edad osciló entre 50 y 80 años, con una media de 68±10 años. La duración media de la enfermedad fue de 10±7 años. De los pacientes con hipercalcemia, 22 eran mujeres postmenopáusicas (92%) y solo dos eran hombres (8%). El hiperparatiroidismo se encontró en 9 pacientes de la serie; solo un paciente tenía una hipercalcemia maligna debido a un mieloma múltiple, y un caso fue consecuencia de una intoxicación por vitamina D. En un paciente la hipercalcemia parecía relacionada con el síndrome calcio-alcalino. En el resto de pacientes, la hipercalcemia fue idiopática (8/24) o el estudio fue incompleto (4/24). No se encontró una relación evidente entre la actividad de la enfermedad y la aparición de hipercalcemia. Conclusión: Al igual que sucede en la población general, el hiperparatiroidismo primario es la causa más común de hipercalcemia en pacientes con AR. En algunos pacientes no se identificaron otros trastornos causantes de hipercalcemia, lo que plantea la posibilidad de una relación causal entre la AR y la hipercalcemia.Objetive: To investigate the prevalence of hypercalcemia in patients with rheumatoid arthritis (RA) and analyze the clinical features and causes of hypercalcemia. Material and methods: Retrospective case?based review study that included 500 patients with RA. Patients with increased calcium levels on at least two occasions were identified. Results: Hypercalcemia was present in 24 of the 500 RA patients (4.8%). The age ranged between 50 and 80 years, with a mean of 68±10 years. The mean duration of the disease was 10±7 years. Of the patients with hypercalcemia, 22 were postmenopausal women (92%) and only two were men (8%). Hyperparathyroidism was found in 9 patients in the series; only one patient had malignant hypercalcemia due to multiple myeloma, and one case was a consequence of vitamin D intoxication. In one patient, hypercalcemia appeared to be related to calcium?alkali syndrome. In the remaining patients, hypercalcemia was idiopathic (8/24) or the study was incomplete (4/24). No obvious relationship was found between disease activity and the appearance of hypercalcemia. Conclusion: As in the general population, primary hyperparathyroidism is the most common cause of hypercalcemia in patients with RA. In some patients, no other disorders causing hypercalcemia were identified, raising the possibility of a causal relationship between RA and hypercalcemia

Abnormal bone turnover in individuals with low serum alkaline phosphatase

The clinical spectrum of hypophosphatasia (HPP) is broad and variable within families. Along severe infantile forms, adult forms with mild manifestations may be incidentally discovered by the presence of low alkaline phosphatase (ALP) activity in serum. However, it is still unclear whether individuals with persistently low levels of ALP, in the absence of overt manifestations of HPP, have subclinical abnormalities of bone remodeling or bone mass. The aim of this study was to obtain a better understanding of the skeletal phenotype of adults with low ALP by analyzing bone mineral density (BMD), bone microarchitecture (trabecular bone score, TBS), and bone turnover markers (P1NP and ß-crosslaps). We studied 42 individuals with persistently low serum ALP. They showed lower levels of P1NP (31.4?±?13.7 versus 48.9?±?24.4 ng/ml; p?=?0.0002) and ß-crosslaps (0.21?±?0.17 versus 0.34?±?0.22 ng/ml, p?=?0.0015) than individuals in the control group. There were no significant differences in BMD, bone mineral content, or TBS. These data suggest that individuals with hypophosphatasemia have an overall reduction of bone turnover, even in the absence of overt manifestations of HPP or low BMD. We evaluated bone mineral density (BMD), bone microarchitecture, and bone turnover markers in patients with low serum levels of alkaline phosphatase. Our results show that these patients have low bone remodeling even in the absence of BMD abnormalities, thus supporting the recommendation of avoiding antiresorptives such as bisphosphonates in these subjects

Haplotypes of intron 4 of the estrogen receptor alpha gene and hip fractures: a replication study in Caucasians

<p>Abstract</p> <p>Background</p> <p>Despite their great impact, few genetic association studies have used hip fractures as an endpoint. However, the association of two polymorphisms on intron 4 of estrogen receptor alpha (<it>ESR1</it>) with hip fractures was recently reported in a Chinese population. The aim of this study was to investigate whether such association is also present in Caucasians.</p> <p>Methods</p> <p>We analyzed those two SNPs and another neighbour SNP located on the exon 4 of <it>ESR1 </it>in 787 patients with hip fractures and 953 controls from Spain.</p> <p>Results</p> <p>The allelic frequencies differed markedly from those reported in Asian populations. Nevertheless, haplotypes including the rs3020314 and rs1884051 loci in intron 4 showed a significant association with hip fractures (omnibus test p = 0.006 in the whole group and 0.00005 in women). In the sex-stratified analysis, the association was significant in females, but not in males. In women, the CA haplotype appeared to have a protective influence, being present in 6.5% of the controls, but only in 3% of patients with fractures (odds ratio 0.39; 95% confidence interval 0.26-0.59; estimated population preventive fraction 3.5%). The inclusion of the rs1801132 SNP of exon 4 further increased the statistical significance of the association (odds ratio 0.17; 95% CI 0.08-0.37; p = 0.00001). Each SNP appeared to contribute independently to the association. No genotype-related differences in gene expression were found in 42 femoral bone samples.</p> <p>Conclusions</p> <p>This study confirms the association of some polymorphisms in the region of exon 4/intron 4 of <it>ESR1 </it>and hip fractures in women. However, there are marked differences in allele frequencies between Asian and Caucasian populations.</p

Genetic and acquired factors influencing the effectiveness and toxicity of drug therapy in osteoporosis

Introduction: Osteoporosis is a highly prevalent skeletal disorder characterized by compromised bone strength, usually related to decreased bone mass and microstructural alterations of bone tissue, predisposing a person to an increased risk of fracture. As other prevalent disorders, osteoporosis is the result of a complex interplay of genetic and acquired factors. Areas covered: We provide an update of recent studies aimed at identifying the clinical and genetic factors that influence the response to drugs used to treat osteoporosis, as well as those determining the risk of two intriguing adverse effects of antiresorptives: osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF). Expert opinion: Several clinical factors have been suggested to increase the risk of a poor drug response, such as advanced age and frailty. Candidate gene studies suggest that some common polymorphisms of the Wnt pathway and farnesyl diphosphate synthase (FDPS), the target enzyme for bisphosphonates, also influence the response to antiresorptives. However, they await for replication in large independent cohorts of patients. Similarly, some genetic and acquired factors may influence the risk of ONJ and AFF. Preliminary data suggest that the risk of suffering these adverse effects may have a polygenic basis

Association of aromatase and estrogen receptor gene polymorphisms with hip fractures

Producción CientíficaSummary Two polymorphisms of the aromatase and estrogen receptor genes appeared to interact to influence the risk of hip fractures in women. Introduction Allelic variants of the aromatase gene have been associated with bone mineral density and vertebral fractures. Our objective was to analyze the relationship between two polymorphisms of the aromatase and estrogen receptor genes and hip fracture

Nuclear receptor NR5A2 and bone: gene expression and association with bone mineral density

ObjectiveThere is growing evidence for a link between energy and bone metabolism. The nuclear receptor subfamily 5 member A2 (NR5A2) is involved in lipid metabolism and modulates the expression of estrogen-related genes in some tissues. The objective of this study was to explore the influence of NR5A2 on bone cells and to determine whether its allelic variations are associated with bone mineral density (BMD).DesignAnalyses of gene expression by quantitative PCR and inhibition of NR5A2 expression by siRNAs were used to explore the effects of NR5A2 in osteoblasts. Femoral neck BMD and 30 single nucleotide polymorphisms (SNPs) were first analyzed in 935 postmenopausal women and the association of NR5A2 genetic variants with BMD was explored in other 1284 women in replication cohorts.ResultsNR5A2 was highly expressed in bone. The inhibition of NR5A2 confirmed that it modulates the expression of osteocalcin, osteoprotegerin, and podoplanin in osteoblasts. Two SNPs were associated with BMD in the Spanish discovery cohort (rs6663479, P=0.0014, and rs2816948, P=0.0012). A similar trend was observed in another Spanish cohort, with statistically significant differences across genotypes in the combined analysis (P=0.03). However, the association in a cohort from the United States was rather weak. Electrophoretic mobility assays and studies with luciferase reporter vectors confirmed the existence of differences in the binding of nuclear proteins and the transcriptional activity of rs2816948 alleles.ConclusionsNR5A2 modulates gene expression in osteoblasts and some allelic variants are associated with bone mass in Spanish postmenopausal women

Calidad de vida en pacientes con fosfatasa alcalina persistentemente baja portadores o no de mutaciones del gen ALPL

Introducción: Los niveles bajos de fosfatasa alcalina (FAlc) en suero son el sello distintivo de la hipofosfatasia, un trastorno debido a variantes patogénicas del gen ALPL. Nuestro objetivo fue determinar la calidad de vida relacionada con la salud en adultos con fosfatasa alcalina baja y explorar las diferencias entre pacientes con y sin mutaciones en ALPL. Material y métodos: Estudiamos 35 pacientes adultos con FAlc persistentemente baja en los que se excluyeron causas adquiridas y se secuenció ALPL. Se compararon con 35 controles de igual edad. Se completaron tres cuestionarios sobre dolor (Brief Pain Inventory, BPI), discapacidad física (Health Assessment Questionnaire Disability Index, HAQ-DI) y calidad de vida relacionada con la salud (36-item Short-Form Health Survey, SF-36). Resultados: Las puntuaciones medias de intensidad e interferencia del dolor en el BPI fueron mayores en el grupo de pacientes (p=0,04 y 0,004, respectivamente). Todos los dominios del instrumento HAQ tendieron a puntuar peor en los pacientes, con diferencias significativas en la puntuación de "alcance" (p=0,037) y la puntuación media general (0,23 frente a 0,09; p=0,029). Los pacientes puntuaron peor que los controles en varias dimensiones del SF-36 (rol físico, p=0,039; dolor corporal p=0,046; rol emocional, p=0,025). Sin embargo, los pacientes con y sin variantes patogénicas puntuaron de manera similar en todas las pruebas, sin diferencias significativas entre los grupos. Conclusiones: Los pacientes con niveles persistentemente bajos de FAlc tienen puntuaciones significativamente peores en dolor corporal y otras dimensiones de calidad de vida relacionadas con la salud, sin diferencias entre pacientes con y sin variantes patogénicas en el gen ALPL. Esto es consistente con la hipótesis de que estos últimos presenten mutaciones en regiones reguladoras, habitualmente no secuenciadas, del gen ALPL

Clinical, biochemical and genetic spectrum of low alkaline phosphatase levels in adults

Background: Low serum levels of alkaline phosphatase (ALP) are a hallmark of hypophosphatasia. However, the clinical significance and the underlying genetics of low ALP in unselected populations are unclear. Methods: In order to clarify this issue, we performed a clinical, biochemical and genetic study of 42 individuals (age range 20–77 yr) with unexplained low ALP levels. Results: Nine hadmild hyperphosphatemia and three hadmild hypercalcemia. ALP levelswere inversely correlated with serum calcium (r = -0.38, p = 0.012), pyridoxal phosphate (PLP; r = -0.51, p = 0.001) and urine phosphoethanolamine (PEA; r = -0.49, p = 0.001). Although many subjects experienced minor complaints, such as mild musculoskeletal pain, none hadmajor health problems.Mutations in ALPL were found in 21 subjects (50%), including six novelmutations. All but one,were heterozygousmutations.Missensemutations were themost common (present in 18 subjects; 86%) and themajority were predicted to have a damaging effect on protein activity. The presence of amutated allelewas associated with tooth loss (48% versus 12%; p=0.04), slightly lower levels of serumALP (p=0.002), higher levels of PLP (p b 0.0001) and PEA (p b 0.0001), aswell asmildly increased serum phosphate (p=0.03). Ten individuals (24%) had PLP levels above the reference range; all carried a mutated allele. Conclusion: One-half of adult individuals with unexplained low serum ALP carried an ALPL mutation. Although the associated clinicalmanifestations are usuallymild, in approximately 50% of the cases, enzyme activity is lowenough to cause substrate accumulation and may predispose to defects in calcified tissues