Volume 5 · Number 2 · June 2013
- Prevalence of hypovitaminosis D and secondary hyperparathyroidism in the Spinal Cord Injury Unit in Gran Canaria. Preliminary study [67-72]
- Risk of fracture associated with states prior to the diagnosis of diabetes mellitus type 2: Nested case-controlled study (DIAFOS cohort) [73-78]
- Divergent effects of TGF-β inhibition in bone metastases in breast and lung cancer [79-84]
- SNPs in the 3’UTR of the RANK gene determine site-dependent osteoporotic fracture [85-92]
In the last few decades clinical research in large population studies has revealed the high prevalence of insufficient levels of vitamin D across the globe1,which, combined with its effects on bone, the muscular-skeletal system, innate and acquired immunity, the cardiovascular system, and the development and function of cells, makes this a first order problem in public health. In fact, low levels of vitamin D are associated significantly with all the causes of morbimortality2.
Prevalence of hypovitaminosis D and secondary hyperparathyroidism in the Spinal Cord Injury Unit in Gran Canaria. Preliminary study
Background: vitamin D deficiency is very common, and has been demonstrated in multiple studies in both the general population and in patients with different pathologies. However, it has been little studied in patients affected by spinal injury.
Objective: to study the prevalence of hypovitaminosis D and the possible development of secondary hyperparathyroidism in a population of patients with spinal injury.
Material and method: transverse descriptive study carried out in 104 patients affected by spinal injury. A clinical history was taken, a detailed physical examination carried out and a blood sample while fasting taken, with the least possible compression, from all patients. The analytical parameters were analysed using automated techniques and the determination of 25-hydroxyvitamin D (25HCC) and parathyroid hormone (PTH) was performed using electroimmunochemiluminescence (ECLIA).
Results: the global mean value of 25-hydroxyvitamin D was 20.1 ± 11.6 n/ml. 84.6% of the patients had blood values of 25-hydroxyvitamin D lower than 30 ng/ml and 62% of all patients showed values lower than 20 ng/ml. The prevalence of vitamin D deficiency was similar in men and women. However, although we found an inverse correlation between levels of PTH and hydroxyvitamin D, only 5.8% of patients ended up developing secondary hyperparathyroidism.
Conclusions: there is a high prevalence of hypovitaminosis D in patients with spinal injury. It is advisable, therefore, to include a study of this metabolite in the care protocol of these patients to correct these deficiencies as and when they are found.
Risk of fracture associated with states prior to the diagnosis of diabetes mellitus type 2: Nested case-controlled study (DIAFOS cohort)
Backgound: In phases prior to the diagnosis of diabetes mellitus type 2 there is an increased risk of cardiovascular disease, but it is not known if this is the case in relation to the risk of fractures.
Objective: To compare the prevalence of fracture in cases of diabetes mellitus and in matched controls.
Material and method: Nested case-control study in a population-based cohort. All patients diagnosed with type 2 diabetes in the period 2006-2011 were included, as were, for each of these patients, two control subjects of the same age, gender, and from the same medical centre, without diabetes. Any fractures, cerebro-vascular accidents and ischemic cardiopathy prevalent in these patients were identified using ICD codes 10. The prevalence of osteoporotic, major and hip fractures, and of cardiovascular disease at the time of diagnosis for the diabetic subjects, and on the same date for the matched controls, were calculated. Using conditional logistical regression the odds ratios (OR) were calculated, adjusting for body mass index, smoking, alcoholism, use of statins, cardiovascular disease and diabetic complications.
Results: 58,931 diabetic patients and 117,862 controls were identified. At the date of diagnosis the diabetic patients had a higher prevalence of cerebro-vascular accident (4.9% vs 3.5%; p< 0.001) and ischemic cardiopathy (8.1% vs 4.7%; p< 0.001). On the other hand, the prevalence of osteoporotic fracture (2.8% vs 2.7%; p= 0.22), hip fracture (0.4% vs 0.4%; p=0.63) and major fracture (1.5% vs 1.5%; p=0.97) was similar in both groups. The adjusted ORs were: 1.2 (CI 95%: 0.96-1.09), 1.08 (CI 95%: 0.90-1.28), and 0.99 (CI 95%: 0.91-1.09), respectively.
Conclusions: The type 2 diabetic patients had a higher prevalence of cardiovascular disease at the time of diagnosis. However, their risk of fracture was similar to the non-diabetic control subjects.
Background: The objective of this study lies in the determination of the validity of transforming growth factor β (TGF-β) as a therapeutic target in models of metastasis deriving from different histological types of lung cancer.
Material and methods: 4-week-old immunodeficient mice inoculated with lung and breast cancer lines were treated with cytokine inhibitor peptide, control peptide or placebo. Weekly bioluminescence and microradiographic measurements were taken to determine the effects of the treatment on tumor burden and metastatic lesions in the long bones.
Results: Treatment with the specific peptide against TGF-β has a protector effect in the bone of animals inoculated with the breast cancer lines, unlike what happens in the control peptide and placebo groups. However, the anti-TGF-β treatment lacks the significant therapeutic effects on the bone metastases which develop in lung cancer bearing animals.
Conclusions: The role of TGF-β as a potential therapeutic target in bone metastasis is highly dependent on the histopathological type and subtype of tumor.
Objectives: The RANK/RANKL/OPG system is involved in the determination of bone mineral density (BMD) and bone microarchitecture. Our study seeks to evaluate if there are SNPs in the 3’UTR region of the RANK gene associated with osteoporotic phenotypes.
Material and methods: Seven genetic variants in 1,098 women from the BARCOS cohort were genotyped, and their association with BMD and osteoporotic fractures evaluated. An interaction with SNP rs9594738 in the RANKL gene which was previously associated with BMD was tested.
Results: None of the SNPs were associated significantly with BMD. SNP rs78326403 was associated with wrist/forearm fractures (Log-additive model odds ratio (OR)=3.12 [IC 95%: 1.69 ; 5.75]; p=7.16×10-4), while SNP rs884205 was associated with fractures of the spinal column (OR=4.05 Recessive; [95% CI: 1.59 ; 10.35]; p=8.24×10-3). Lastly, an interaction was detected between SNP rs9594738 from RANKL and rs78326403 from RANK on the presence of fracture (p=0.039). The analysis of the effects of combined genotypes rs9594738 and rs78326403 pointed to an increase in the prevalence of fractures in subjects with a greater number of unfavourable alleles, the ORs being 2.76 [95% CI: 1.30 ; 5.81]; p=0.007) and 5.14 [95% CI: 1.37 ; 15.67]; p=0.007) for 2 and ≥3 unfavourable alleles respectively, in comparison with none/1.
Conclusions: Two SNPs in 3’UTR from the RANK gene predispose to site-dependent osteoporotic fracture. An interaction with SNP rs9594738 from RANKL suggests an additive effect of BMD and bone strength.
The case is described of a 34 year old patient with Cushing’s disease diagnosed as a result of having multiple pathological vertebral fractures after giving birth. The sudden appearance of acute fractures in five vertebral bodies, the phenotype characteristics of the patient and her medical history pointed to a diagnosis of Cushing’s syndrome, a condition which rarely coincides with pregnancy. After a resection of the hypophysary adenoma and the start of treatment with teriparatide, the patient experienced notable clinical and densitometric improvement. This case demonstrates the importance of suspecting a bone metabolism disorder in the presence of pathological fractures in young patients, even more in certain states, such as pregnancy or lactation.
Biomechanics and bone (& II): Trials in different hierarchical levels of bone and alternative tools for the determination of bone strength
For a greater understanding of the mechanical properties of bone as a whole, it is first necessary to determine the behaviour of each of the components in an individual way at its corresponding structural level, as well as its overall involvement. This is the basis of the theory of hierarchical structure of bone, which involves its division into different structural levels. In this work we review, level by level, this hierarchical structure, reviewing the different mechanical trials which are applied to each of the structure. In addition, the methods for the determination of bone strength alternative to the classic mechanical trials are presented, which in recent years have been contributing significantly to the mechanical understanding of bone.
The possible association between osteoporosis and osteoarthritis represents an ongoing matter of debate. It was considered, for decades, that both diseases were mutually exclusive due to the anthropometric characteristics and the difference in bone mass that patients with osteoporosis and osteoarthritis often present. However, in recent years, it was pointed out that both processes can coexist, and even that they may have a direct relationship. In this paper we review some aspects of the association between both diseases from a temporal perspective.