Volume 9 · Number 2 · June 2017
- Assessment of the predictive capacity of the Garvan calculator of 10 year risk of fracture in a Spanish population [55-61]
- Medical care circuits for postmenopausal patients in Spain [62-71]
- Genetic analysis of steroid pathway enzymes associated with adverse musculoskeletal effects of aromatase inhibitors [72-81]
- Screening and biochemical characterization of primary hyperparathyroidism in Guayaquil (Ecuador) [82-88]
Loss of bone mass is only part of the syndrome which, in addition to densitometric osteoporosis, sarcopenia and other risk factors, eventually contributes to fragility fracture. The low sensitivity and specificity of bone mineral density (BMD) measurement in predicting fracture risk has led to the development of tools that include several known risk factors such as demographic variables, physical examination, personal and/or family history of fracture, presence of diseases or medications with influence on bone metabolism and risk factors for falls . Some of these algorithms for predicting the risk of fracture have not been validated in external populations, others lack methodological deficits and only a few have been integrated into national clinical guidelines for osteoporosis.
Validation, both internal and external, is one of the keys to developing a risk calculator. In particular, external validation generalizes the scale to populations beyond those in which it was generated. The work of Reyes Domínguez et al. , published in this issue of the Journal of Osteoporosis and Mineral Metabolism, is the first in Spain to validate the Garvan calculator in a sample of 121 individuals without basal densitometric osteoporosis, monitored over 10 years and who had not received anti-osteoporotic treatment during that time.
Assessment of the predictive capacity of the Garvan calculator of 10 year risk of fracture in a Spanish population
Introduction: Several calculation tools or scales have been developed in recent years to assess the risk of fracture due to long-term fragility. The Garvan calculator has not been validated in the Spanish population. This study aims to observe their predictive capacity in a population sample of the Canary Islands and, therefore, of the Spanish population.
Material and Methods: We included 121 patients who were followed up for 10 years in our consultations. All were assessed the risk of fracture using the Garvan calculator and based on the data obtained in the first visit.
Results: Of the 121 patients, 30 suffered at least one osteoporotic fracture over the 10-year follow-up period. The group of patients with fractures had on the Garvan scale an average risk value to suffer any fracturing fracture of 27%, compared to 13% of those who did not suffer fracture (p<0.001). The area under the corresponding ROC curve was 0.718 (CI-95% = 0.613 ; 0.824). Based on this, the estimated optimal cut-off point to consider a high risk fracture was 18.5%. This value corresponded to a sensitivity of 0.67 (CI-95% = 0.47 ; 0.83) and a specificity of 0.67 (CI-95% = 0.56 ; 0.77). Conclusions: Our results show that the Garvan scale adequately predicts the risk of 10-year osteoporotic fracture in our population. A value lower than 18.5% would allow us to establish a low fracture risk and could be used as a screening tool.
Objectives: To reach a consensus on the medical care circuits of patients with postmenopausal osteoporosis (PMO), including derivation and management (assessment tools and medical tests), identifying profiles according to the opinion of bone metabolism experts, from Spain’s Health Service.
Material and methods: The Delphi technique was used with two successive consultation rounds, with 38 experts in PMO management belonging to 14 scientific societies taking part in the study. Review of literature and the opinion of the scientific committee rounded out the questionnaire. The experts expressed their “desire” (1=total rejection, 9=stronger desire) and “forecast” (1=will absolutely not occur; 9=will occur with maximum probability) about the issues raised. A consensus was reached when 75% or more of the participants scored 1-3 (disagreement) or 7-9 (agreement). In addition, experts were divided up into 3 discussion groups to complement the information according to patient profiles found previously in the Delphi method.
Results: Consensus was reached on 75% of the questions. The experts established three profiles of PMO patients: no fracture, vertebral fracture and non-vertebral fracture, as well as the diagnostic and therapeutic resources recommended for these patients.
The patient without a fracture should be managed in Primary Care or Rheumatology and scales will be used to evaluate fracture risk in early stages of the disease. The patient with chronic vertebral fracture should refer to Rheumatology and Rehabilitation, and will be Rheumatology, whereas the patient with acute vertebral fracture should be treated in Orthopedic Surgery, and this is how it will possibly happen. Diagnosis of vertebral fracture patients will be based mainly on x-rays.
To assess progress, questionnaires on the functional capacity and pain scales are recommended. However, these will not be used due to the lack of time involved. The patient with non-vertebral fracture should be and will be referred to Orthopedic Surgery, with 3-4 radiographs recommended to ensure fracture consolidation.
Conclusions: Delphi method results indicate that referral of PMO patients are concentrated in Primary Rheumatology, when there is no fracture, and Orthopedic Surgery, in the case of fracture.
Genetic analysis of steroid pathway enzymes associated with adverse musculoskeletal effects of aromatase inhibitors
Objetives: Identify putative functional variants in the CYP11A1 and CYP17A1 genes associated with musculoskeletal effects (accelerated bone mass loss and arthralgia) derived from treatment with aromatase inhibitors (AI).
Material and methods: The B-ABLE cohort is a prospective study of postmenopausal women with breast cancer undergoing AI treatment. Bone mineral density in the lumbar spine and femoral neck was measured by densitometry and joint pain using visual analogue scale. From single-nucleotide polymorphisms (SNPs) in genes CYP11A1 (rs4077581, rs11632698 and rs900798) and CYP17A1 (rs4919686, rs4919683, rs4919687, rs3781287, rs10786712, rs6163, rs743572), previously associated with musculoskeletal events, haplotypes were constructed for each pacient from the cohort, and those haplotypes that showed greatest phenotypic differences were chosen (p<0.05). Within each haplotype, patients with extreme phenotypes were chosen for the sequencing of respective genes and identifying functional genetic variants. Finally, a multiple linear regression analysis was carried out considering the models of dominant, recessive and additive genetic inheritance.
Results: No mutation was found in coding regions. A genetic variant (D15S520), in the basal promoter region of gene CYP11A1, was found associated with femoral neck bone loss at 24 month of AI treatment.
Conclusions: Variants in regulatory regions of the CYP11A1 gene could modulate the expression of this gene, thus explaining part of the phenotypic variability found in bone loss of patients undergoing AI treatment.
Objectives: To determine the prevalence of primary hyperparathyroidism (HPTP) using PTH and Ionic calcium screening in a population sample of Guayaquil (Ecuador).
Materials and methods: Prospective, cross-sectional study carried out between January 1, 2009 and November 30, 2014 of 13,860 people who attended routine control tests. All were tested in serum parathyroid hormone (PTH), ionic calcium, serum creatinine and the 25 (OH) total vitamin D (total VD). The diagnosis of HPTP was confirmed if PTH or Ionic calcium levels remained high at least in two different occasions. We excluded patients with raised serum creatinine, vitamin D insufficiency, malabsorption, chronic liver disease, or those receiving treatments that alter phosphocalcic metabolism.
Results: 61 cases were found with raised PTH on at least two different occasions. Among these, 34 presented vitamin D insufficiency and were excluded from the analysis. In 27 cases (4 men and 23 women) the diagnosis of HPTP was confirmed. The average age for women was 64.5±15.4 years and men of 71.3±12.8 years; average PTH values were 115±24.2 pg/ml; Ionic calcium, 5.15±0.4 mg/dl; total VD, 47.1±20.2 ng/ml; and serum creatinine 0.84±0.2 mg/ml; prevalence of HPTP corresponds to 2 cases per thousand adults (95% CI: 1.71-2.18). The greatest increase in prevalence occurred in women aged 60 years.
Conclusion: PTH prevalence in this sample is low compared to that reported in international series, being higher in advanced ages and in women. With the proposed screening for PTH and ionic calcium, we detected the normocalcemic form of HPTP in most cases.
In recent years, progress has been made in regulating skeletal development and maintenance of bone mass of the adult by the hypothalamus-pituitary-thyroid axis. Studies have been carried out into the effect of thyroid hormones on the osteoblasts, osteoclast and the chondrocyte. This research has led to better genetic knowledge into the physiology of the cellular action of these hormones. Recently, possible D2 deodinase interventions in osteoporosis have been proposed. The link between bone mineral dignity, bone quality and the risk of fractures with thyroid hormones in normal postmenopausal women suggest a role for these hormones, even within the range of normal thyroid, in these diseases.
On the other hand, the incidence of differentiated thyroid cancer, experimental in vivo thyroid hormone suppression by therapy, recurrent disease, has increased significantly. There are management guides, but it is clear that the secondary derivatives require a precise balance-adjusted indication, risk-benefit ratio of thyroid hormone dosage, prescribed long term, especially in cases of low tumor aggressiveness, advanced age and even in fragile patients. High risk patients should be referred for a bone densitometry, to consider treating future fractures. Prevention of osteoporosis, particularly in postmenopausal women, is highly desirable and should include adequate diet in calcium and vitamin D supplementation if necessary. There is still no consensus on osteoporosis treatment in the patient with thyroid cancer and suppressive treatment, but the indicated criteria for postmenopausal osteoporosis seem to be applicable in general.