Volume 5 · Number 4 · December 2013
- Blood sclerostin and Dkk-1 in patients who start treatment with glucocorticoids. Preliminary results [127-132]
- Response of osteoblasts to compounds of strontium or calcium: proliferation, differentiation, mineralisation and whole genome response [133-140]
- The reality of osteoporosis in patients hospitalized in Internal Medicine [141-145]
- The history of SEIOMM (1987-2013) [151-157]
The association between an excess of glucocorticoids and osteoporosis was indicated more than 80 years ago by Harvey Cushing when describing the disease which takes his name. Subsequently, after the introduction of the glucocorticoids as anti-inflammatory drugs, it was confirmed that exogenous hypercortisolism was also detrimental to the skeleton, in such a way that steroidal osteoporosis is now considered to be the most common form of secondary osteoporosis in our ambit1. Osteopenia induced by corticoids affects predominantly trabecular bone and is most intense during the first months of treatment, when more than 10% of bone mass may be lost2. In addition to inducing the loss of bone, the glucocorticoids alter its quality, which would explain the notable increase in fractures (nearly 75%) during the first three months of treatment, even before bone mineral density falls.
Blood sclerostin and Dkk-1 in patients who start treatment with glucocorticoids. Preliminary results
Background and objectives: The Wnt pathway and its inhibitors (sclerostin and Dkk-1) have a primary role in the regulation of bone mass and osteoblastogenesis. The objective of this study was to analyse the effect of treatment with glucocorticoids (GCC) on the inhibitors of the Wnt pathway and their relationship with bone mass and the parameters for bone turnover.
Methods: A transverse study including 15 patients (9 women and 6 men) with an mean age of 51±21 years at the start of treatment with GCC (≥ 7.5 mg/day, ≤ 6 months). Levels of sclerostin, blood Dkk-1 and blood markers for bone turnover (procollagen 1 N-terminal propeptide [P1NP], osteocalcin [OC], and carboxy-terminal telopeptide of collagen type 1 [CTX] ) were determined, and bone densitometry ( DXA) in the lumbar spine was carried out, in all patients. The results were compared with a control group.
Results: The mean dose of glucocorticoids was 58 ± 21 mg/day, in the majority of patients (73%) indicated by idiopathic thrombocytopenic purpura. The patients treated with glucocorticoids had a reduction in the parameters for bone formation compared with a control group (OC: 7.4 ± 2.8 vs 24.4 ± 6.2 ng/ml, p<0.01) and a reduction in blood Dkk-1 (29.6 ± 23.6 vs 48.3 ± 15.6 pmol/L, p=0.02). No significant differences were observed in values for blood sclerostin, although this correlated positively with the dose of GCC received and lumbar bone mineral density.
Conclusion: Contrary to what is seen in experimental studies, the start of treatment with glucocorticoids is associated with a reduction in blood levels of Dkk-1. These results indicate the necessity of analysing these inhibitors and their relationship with remodelling and bone mass during this process over the long term.
Response of osteoblasts to compounds of strontium or calcium: proliferation, differentiation, mineralisation and whole genome response
Background: The mechanisms which trigger osteogenesis are not yet clear. The objective of this study was to evaluate the role of strontium and calcium, provided in different molecular forms, as inductors of different mechanisms of osteoblast stimulus, including proliferation, differentiation and mineralisation of preosteoblast cells. The whole genomic response was also investigated using the microarray technique.
Methods: An experimental study was designed with murine preosteoblast cells MC3T3-E1, which were stimulated for 3 hours and 7 days. Biochemical and genome gene expression studies of mouse (Affymetrix) were carried out.
Results: Strontium bonded with ranelate (SrRn) was the most powerful inductor of the capacity of mineralisation in comparison with the other compounds used (2.55 times that of the control). The studies of whole gene expression showed that after 3 hours 2030 genes change, of which 1644 are specific to this phase. On the other hand, after 7 days of treatment only 329 genes change, of which 147 are specific. The biological processes most enriched after 3 hours are those involved in the regulation of transcription (147 genes), metabolic processes (140 genes) and protein phosphorylation (44 genes) among others, while at 7 days these are changes relating to the cell cycle (18 genes) and carbohydrate metabolism in general (12 genes).
Conclusion: Strontium bonded with the ranelate anion performed as the most powerful inductor of osteogenesis compared with other anions such as chloride or the hydroxides. The stimulation for 3 hours showed greater changes in gene expression in comparison with 7 days. The biological processes affected may be useful in speculating on the signalling cascades involved in the activation of the osteoblast, and on new molecular targets for therapeutic purposes.
Purpose: a) to know the prevalence of previous osteoporosis and vertebral fractures in patients admitted to an Internal Medicine department from a third-level hospital; b) to determinate the proportion of patients discharged with a diagnosis of osteoporosis, and the percentage of those receiving treatment; c) to quantify the risk of fracture by applying the FRAX calculation tool; and d) to know the serum levels of 25OHD in these patients.
Patients and methods: Retrospective study, based on the review of clinical charts of all the patients admitted to the Internal Medicine department of Marqués de Valdecilla University Hospital, during April 2012. The information was gathered by a standardized protocol, including demographic, clinical, radiological and laboratory variables.
Results: Three hundred patients were studied (mean age, 80 years). Thirty-four (11.3%) had a previous diagnosis of osteoporosis and 14 (4.8%) of them were, or had been, on treatment. A diagnosis of osteoporosis, in the hospital discharge report, was noted in 14 patients. No treatment was prescribed in one of them. According to the FRAX calculation tool, mean risk for major osteoporotic fracture was 10.5%, and mean risk for hip fracture was 5.4%. Mean serum 25OHD level was 16 ng/ml, and more than 80% of patients had values below 20 ng/ml.
Conclusion: Osteoporosis is an underdiagnosed and undertreated disease, in patients admitted to an Internal Medicine Department, whatever the reason. Moreover, we have observed a high prevalence of 25OHD deficiency among these patients. Hospitalization can represent an excellent opportunity for the internists and other clinicians, to pay attention to the presence of osteoporosis and its related complications.
Bone metastases are common in advanced cancer, occurring up to 75% of patients with advanced breast cancer. Complications of bone metastases include bone pain, hypercalcemia and skeletal-related events (SERs), such as fracture, need for radiation or surgery to bone, or spinal cord compression.
A 50 year-old patient with advanced breast cancer, who has multiple skeletal-related events and poorer overall quality of life.
During the 1980s, the medical professionals associated with diseases of the locomotor apparatus began to pay attention to metabolic bone diseases, and among these, a pathology very common in advanced age, osteoporosis, which, until this time had passed almost unnoticed due to the absence of precise methods of diagnosis. Bone fractures, to a great extent brought on by osteoporosis, were frequent and provoked disorders and disabilities, above all in women after the menopause. The appearance of highly precise methods for the diagnosis of osteoporosis and of efficacious drugs for its treatment led to an increase in interest in this pathology on the part of medical specialists directly or indirectly associated with the locomotor apparatus such as internists, rheumatologists, endocrinologists, gynaecologists and nephrologists. In Spain this situation resulted in the formation of the Spanish Society for Bone and Mineral Metabolism Research (SEIOMM) and led to a pharmaceutical company offering DXA densitometry at 14 Spanish hospitals, facilitating the diagnosis and study of osteoporosis.