Volume 3 · Number 1 · March 2011
- Changes in bone microarchitecture in rheumatoid arthritis. Study using microCT [9-16]
- Evaluation of the risedronate efficiency 75 mgs versus generic alendronate 70 mgs, in women with post-menopausal osteoporosis and previous vertebral fractures in Spain [21-29]
- Preliminary study of osteoblasts in peripheral blood in the population of infants and adolescents* [31-34]
- Treatment of Paget’s disease of bone [35-40]
- Dyslipidemia and bone metabolism. A common bond of the osteoporosis and the atherosclerosis? [41-50]
Maxillary osteonecrosis (MON) is a disease which has appeared recently as a serious complication in patients suffering from neoplasms or other chronic diseases. MON has been associated with the use of powerful diphosphonates, for which reason many authors have named the disease secondary osteonecrosis of the mandible due to biphosphonates1-5.
This is a relatively new disease, which means that there is not yet unanimity on many of its aspects. For a start, there is no clear and universally accepted definition of MON. A panel of experts from the American Society of Bone and Mineral Research (ASBMR)2 recently recommended using the definition “an area of exposed bone which persists for more than 8 weeks in the absence of earlier irradiation and/or metastasis in the mandible”. The American Academy of Mouth and Maxillofacial Surgeons published a similar definition: a patient may have MON if they comply with 3 requirements: 1) current or previous use of biphosphonates; 2) the presence exposed or necrotic bone for a minimum of 8 weeks; and 3) an absence of maxillary radiotherapy. At this point should insist that the correct name for the disease is maxillary necrosis and not necrosis of the mandible, given that there is frequently also affectation of the upper maxilla6.
Introduction: The objective of this study is to analyse the bone microarchitecture in rheumatoid arthritis (RA) in a series of biopsies of the iliac crest carried out previously in patients not having had earlier treatment with glucocorticoids, using microCT analysis.
Material and method: 14 bone specimens were obtained, taken from the iliac crest of patients with RA with no previous treatment with glucocorticoids. None of these patients was diagnosed with a disease or was taking medicines which could compromise bone mineral metabolism. A complete clinical history was taken, and a blood analysis carried out, including the rheumatoid factor. The specimens were embedded in methyl-methacrylate and studied with a microCT eXplorer Locus SP scanner. The acquisition parameters were: 80 kVp/80 μA, thickness of aluminium filter:10-3 inches, FOV ≈ 2×2 cm, mode of acquisition of 360°, 720 views, 4 frame averages/view, exposure time 1.700 ms, voxel resolution: 28 μm. A region of interest (ROI) was selected by means of interpolation, avoiding cortical bone. An automatic segmentation process (thresholding) was used to differentiate and segment the hematopoietic bone tissue. The microarchitectural parameters were generated automatically by computer using parallel-plate algorithms. The results were compared with 14 specimens from healthy controls of similar age and sex using Student’s test for unpaired samples. The statistical significance was p< 0.05.
Results: The fraction of bone volume (BV/TV) was significantly lower in those patients with RA than in the healthy controls (p< 0.05). The trabecular thickness (Tb.Th) was higher in the controls. The trabecular separation (Tb.Sp) was higher in those specimens with RA (p< 0.05). The trabecular connectivity (Tb.N) was significantly greater in the control specimens (p< 0.05).
Conclusions: The patients with RA have worse trabecular bone quality and low trabecular connectivity. The microCT scanner is a quick and powerful tool for the study of trabecular microstructure.
Evaluation of the risedronate efficiency 75 mgs versus generic alendronate 70 mgs, in women with post-menopausal osteoporosis and previous vertebral fractures in Spain
Introduction: The objective is to assess the cost-effectiveness of risedronate 75 mg 2 consecutive days/month vs generic alendronate 70 mg weekly, during one year in 75 years old females with post-menopausal osteoporosis and previous vertebral fracture.
Methods: A cost-effectiveness analysis under Health National System perspective has been developed to assess clinical (hip fracture prevention and quality adjusted life years gained) and economic consequences (€ 2010) during 5 years following one year treatment with both alternatives. Drug effect has been considered during the one year of drug administration. Epidemiology data and unitary costs were derived from Spanish literature.
Results: In a cohort of 1.000 females, (75 years old) with post-menopausal osteoporosis and vertebral fractures, risedronate 75 mg vs alendronate avoid 10 hip fractures, with 9.983€/hip fracture avoided cost. Aditional QALY gained are 4 with an incremental cost of 99,83€. Incremental cost-effectiveness ratio (ICER) is 24.957€ per QALY gained with risedronate 75 mg vs generic alendronate 70 mg.
Conclusion: In the treatment of females with post-menopausal osteoporosis and previous vertebral fracture, risedronate 75 mg 2 consecutive days/month compared to generic alendronate 70 mg weekly is an efficient strategy in Spain.
The presence of osteoporosis in adult life is conditional on the adequate development and formation of bone during growth in infancy and adolescence and the successive loss which occurs throughout life. Knowledge regarding bone tissue cells and their precursors in stages of growth is scarce, given the difficulties in obtaining samples of this tissue. Recent studies suggest a method of obtaining osteoblast line cells from peripheral blood. The main objective of this work has been to quantify the osteoblast line cells in the peripheral blood of infants and adolescents, as well as noting any possible differences according to the stage of growth.
38 subjects were studied, 16 children (between 4 and 12 years of age) and 12 adolescents (aged between 12 and 18 years). Osteoblast precursor cells in peripheral blood were analysed using the flow cytometry technique. The preliminary results show higher levels of preosteoblastic cells in the youngest age group: 4.17% ± 0.92 vs 2.03% ± 0.48, p= 0.021. There is a negative correlation between the percentage of preosteoblastic cells and age r= -0.488 and weight r= -0.530, p< 0.05. In summary, this technique allows us to quantify preosteoblasts in peripheral blood, and we show that they have a higher percentage, the lower the age, during the period of infancy and adolescence.
Paget’s disease of bone (PDB) is a chronic and focussed skeletal disorder, whose cause is unknown. The disease is located in the osteoclasts, which increase in number, size and activity. Bone turnover accelerates, with an increase in bone resorption, followed by excessive and disorganised formation. The result is bone which is not laminar (plexiform bone) highly vascularised, increased in volume, less compact and more susceptible to fracture or deformation. It is usually diagnosed at over 60 years of age, being infrequent below 40 years of age. It slightly predominates in males. It is the most common metabolic bone disease after osteoporosis1.
It is considered to be a multifactorial disease with the involvement of environmental and genetic factors.
Its main clinical manifestations are bone deformity and pain. During its evolution various complications may appear, the most frequent being degenerative arthropathy in its vicinity, neurological changes due to compression, fractures, cardiac pathology, disorders of the metabolism and of bone remodelling.
The diagnosis is based on clinical manifestations, raised levels of biochemical markers for bone remodelling (essentially, alkaline phosphatase – AP) and radiology.
There is no curative treatment, but the anti-resorptives, especially the diphosphonates, are efficacious in controlling the activity and progression of the disease. The therapeutic objectives are to eliminate bone pain, normalise bone remodelling, re-establish normal bone structure and prevent recurrence and complications.
The magnitude of the public health problem related to cardiovascular disease (CVD) and osteoporosis has been widely documented in the medical literature in the last decades, and common pathogenic links have been recently proposed. Dyslipidemia is one of the most important risk factors in the genesis and development of atherosclerosis, and therefore of CVD, which remains the leading cause of cardiovascular mortality in western countries. On the other hand, osteoporosis and its more serious consequence; fracture, represent a true epidemic nowadays. In this context, the relationship between dyslipidemia and bone metabolism has been addressed by several investigators, although results have been inconsistent. The purpose of this paper is to review the medical literature about the possible association between dyslipidemia and several aspects of bone metabolism.
In the last few years there has been a notable interest in vitamin D, not only due to its crucial importance in bone mineral metabolism, but also for its effects outside the bone, which, every day, are becoming better known.
Similarly, the existence of low blood levels of vitamin D, lower than what is desirable, has been found in different populations, both healthy and sick, and there is a discussion as to what would be the optimum levels of vitamin D in the blood.
For all these reasons, the Spanish Society of Bone and Mineral Metabolism Research (Sociedad Española de Investigación Ósea y Metabolismo Mineral – SEIOMM), jointly with all the scientific societies involved in the study of bone metabolism, have produced this position document on the requirements and optimum levels of vitamin D.
Material and method
The content of this document was developed in the following stages:
a) Meeting of a group of experts in osteoporosis to discuss and agree the relevant clinical questions related to vitamin D (Table1).
b) Creation of a systematic review team, formed by two experts in bone mineral metabolism who carried out the search, a standardised review, critical analysis and tabulation of the articles which had been published in Spanish and English between January 2000 and May 2010. The search was carried out using the MeSH (Medical Subject Headings) terms of the National Library of Medicine of the US National Institutes of Health, related to the topic. Using these terms, the following databases were consulted: PubMed, Medline Plus, Cochrane Library, Up to Date and OVID. Similarly, an ascending search was made of the previously published guides to clinical practice relevant to the topic, as well as articles suggested by the group of experts.
c) Those articles which provided the best level of evidence for each of the questions raised were included (Table 2).
d) Subsequently, following on from the results obtain in the search, a draft of the position document was put together by the group of clinical experts to respond to the questions previously formulated and to provide a consensus on recommendations, taking into account social, economic and health repercussions. In cases of disagreement, a majority opinion was formed, leaving the absence of unanimity on record.