Volume 4 · Number 4 · December 2012
- Variables which influence concentrations of sclerostin in patients with diabetes mellitus type 2 and its association with bone metabolism [109-116]
- Osteogenic effects of PTHrP (107-111) loaded in bioceramics in a model of bone regeneration after a cavitary defect in the femur of a rabbit [117-126]
- Osteointegration and biocompatibility in vivo of bio-inspired silicon carbide ceramics in an experimental model in rabbits [127-132]
- Expression of RANKL and OPG in primary osteoblasts [133-140]
In the current number, García-Martín et al.1 from the working group of Dr. Muñoz of Granada report that blood levels of sclerostin – the protein coded for by the gene SOST, which inhibits the osteoblast Wnt pathway – depend on the sex, the age and the renal function of patients with diabetes mellitus type 2 (DM2). They also demonstrate, contrary to expectations, a negative relationship with the markers for bone remodelling, and a positive relationship with bone mineral density (BMD). Finally, they show that blood levels of sclerostin are lower in patients with DM2 and osteoporosis irrespective of the presence or absence of fractures.
DM2 is a disease of high prevalence – up to 12-15% of the adult population in our country2 – and with an enormous impact on morbi-mortality and quality of life. Its relationship with micro-vascular complications – retinopathy, nephropathy and diabetic neuropathy – and macro-vascular complications – coronary artery, peripheral arterial and cerebrovascular disease – is well known. Most recently, new complications have been recognised to be clearly related to diabetes, among which osteoporosis or diabetes-related metabolic bone disease is a notable example.
Variables which influence concentrations of sclerostin in patients with diabetes mellitus type 2 and its association with bone metabolism
Background and objectives: Diabetes mellitus type 2 (DM2) is associated with an increased risk of fractures whose underlying mechanisms are complex. The objective of this study was to analyse the variables which influence blood concentrations of sclerostin and the relationship with bone metabolism in a group of DM2 patients.
Patients and methods: A transversal study of 76 patients with DM2. Clinical data, basic biochemical parameters, calciotropic hormones, markers for bone remodelling, vertebral X-rays and bone mineral density (BMD) were gathered. Blood concentrations of sclerostin were determined using ELISA (Biomedica, Austria).
Results: The males had higher concentrations than the females (63.15±27.03 vs 43.14±17.08 pmol/L, p<0.001). We found positive relationships between sclerostin and age in males with DM2 (r=0.338, p=0.031) and between sclerostin and creatinine in the whole sample (adjusted for age: r=0.362, p<0.001). Also, it had a negative relationship with bone alkaline phosphatase (BAP) (r=-0.259, p=0.029), carboxy-terminal telopeptide of type 1 collagen (CTX) (r=-0.356, p=0.002) and tartrate-resistant acid phosphatase 5ββ(TRAPβ) (r=-0.289, p=0.013). BMD in the lumbar spine, femoral neck and total hip were positively associated with sclerostin (r=0.373, r=0.492, r+0.524, p<0.001) adjusted for age. Blood levels of sclerostin were lower in patients with DM2 and osteoporosis than those who were non-osteoporotic (42.96±19.16 vs 56.95±25.98 pmol/L, p=0.041).
Conclusions: Sex, age and renal function are determining factors of levels of sclerostin in the circulation of patients with DM2. There is a negative relationship with remodelling markers and a positive one with BMD. Blood levels of sclerostin are lower in patients with DM2 and osteoporosis.
Abbreviations: FN: femoral neck; LS: lumbar spine; TH: total hip; CTX: carboxy-terminal telopeptide of type 1 collagen; DXA: dual X-ray absorptiometry; BAP: bone alkaline phosphatase; GF: glomerular filtration; BBG: basal blood glucose; HbA1c: glycated haemoglobin; BMI: body mass index; PTH: parathormone; OC: osteocalcin; TRAPβ: tartrate-resistant acid phosphatase 5β; 25(OH)D: 25-hydroxyvitamin D.
Osteogenic effects of PTHrP (107-111) loaded in bioceramics in a model of bone regeneration after a cavitary defect in the femur of a rabbit
Introducción: Parathyroid hormone-related protein (PTHrP), which is abundant in bone tissue, is an important modulator of bone formation. It has been shown that PTHrP (107-111), called osteostatin, loaded into mesoporous ceramic material SBA-15 exerts osteogenic action in vitro.
Objective: To confirm if this material and a functionalised version of the same material (C8-SBA-15) promote bone regeneration in a model of a cavitary defect in a rabbit femur.
Materials and methods: Histological, immunohistochemical and computerised microtomography (µCT) studies were carried out in order to achieve the aims of the study.
Results: After the implantation of the biomaterials no significant levels of inflammation or bone resorption were observed (at 4 and 8 weeks). At 8 weeks the bioceramics not loaded with osteostatin were found to be separated from the bone medulla by a fibrous capsule which diminished significantly in the presence of the peptide. An increase was observed (using µCT) in bone neo-formation at different distances from the biomaterials, principally in those loaded with the osteostatin. These results were also confirmed by immunohistochemistry of osteoblast markers.
Conclusion: Our results suggest that the use of these osteostatin-loaded bioceramics are a good strategy for accelerating bone regeneration.
Osteointegration and biocompatibility in vivo of bio-inspired silicon carbide ceramics in an experimental model in rabbits
Background: The new generation of materials for implants should imitate the hierarchical structures found in nature. Bio-inspired silicon carbide ceramic (bioSiC) is a ceramic produced from wood, which has a similar structure to bone, with a unique property of interconnected porosity, which allows the internal growth of tissue and favours angiogenesis.
Objectives: To evaluate the biocompatibility and osteointegration of bioSiC in femoral bone defects in an experimental model in rabbits.
Material and methods: 36 cylinders of bioSiC were obtained through pyrolysis of sapelli wood and infiltration with molten silicon of the resulting carbon preform. Eighteen cylinders were coated with Si-HA by pulsed laser deposition. The cylinders were implanted in femoral condyles of rabbits which were sacrificed at 1, 4 or 12 weeks. The samples were analysed histologically using an optical microscope and computerised microtomography to assess bone growth.
Results: The bioSiC implants showed good osteointegration, there being both outward growth (ongrowth) and inward growth (ingrowth). At 4 weeks from implantation the integration was almost complete, with no difference from that seen at at 12 weeks. The coating did not improve the value of any parameter with respect to the non-coated implants.
Conclusions: BioSiC ceramics produced from porous wood have good osteointegration and their interconnected porosity is colonised by bone tissue. In addition, they do not require the bioactivity of a coating to improve the apposition of neoformed bone. BioSiC stands as a material to be taken into account in biomedical applications.
Objective: Osteoblasts are specialized cells responsible for bone formation. Furthermore, these cells modulate osteoclast formation and maturation, mainly by the production of RANKL and OPG. We previously reported that the bone tissue of osteoporotic patients showed increased RANKL expression and RANKL/OPG ratio when compared to osteoarthritic patients. Thus we decided to explore whether this aberrant expression may be related to an abnormal expression of these genes by osteoblasts. The aim of this study was to explore the transcriptional levels of these factors in primary osteoblasts.
Methods: Primary human osteoblasts (hOBs) were obtained by the primary explant technique from bone tissue of patients undergoing hip replacement surgery for hip fractures (n=28) or osteoarthritis (n=26). Patients with secondary osteoporosis, fractures due to high-energy trauma or secondary osteoarthritis were excluded. RANKL and OPG gene expression was explored by real time quantitative PCR.
Results: No statistical differences in RANKL and OPG gene expression were found along the in vitro mineralization of hOBs. Interestingly, OPG transcriptional levels were markedly higher than RANKL levels. However, no differences in the transcriptional levels of RANKL and OPG were observed between both groups.
Conclusions: Overall, our data confirm that osteoblasts produce RANKL and OPG. However, our results suggest that the gene expression differences found in the osteoporotic and osteoarthritic bone tissue are not explained by the intrinsic characteristics of osteoblasts.
In thyroid carcinoma, distant metastases are infrequent (10-15% of the follicles). The most common sites are the lungs, bones (appearing in the form of lytic lesions), the brain, the liver, the bladder and the skin. The diagnosis of follicular carcinoma through a metastatic complication is exceptional, but it should be considered in the differential diagnosis of a pathological fracture. We present three cases of exceptional occurrence.
Prostate cancer is one of the most frequent cancers in man and it’s incidence is growing constantly due to early diagnosis that is now being made by determining levels of PSA in the general health controls. The most common site of metastasis is bone, and these lesions are frequently symptomatic, causing pain, debility, and functional impairment. Skeletal metastases in men with prostate cancer are usually osteoblastic although increases in bone resorption have been consistently demonstrated. A 49 years old man with a recent diagnosis of prostate cancer was admitted to Emergency Department for right thoracic pain. The physical examination showed pain of mechanical characteristics corresponding to the 5th-7th ribs. The chest radiography showed absence of the 6th rib.
The clinical manifestation of primary hyperparathyroidism (PHPT) as a hypercalcemic crisis should give rise to the consideration of a differential diagnosis between various different clinical processes for variable prognosis and the consideration of an underlying thyroid pathology.
Cystic parathyroid adenoma is one of its most infrequent causes in the group of glandular cystic neoplasms in the cervix.
The diagnosis of its functional character, supported by the determination of calcemia, blood and intracystic immunoreactive parathormone (PTHi), and the interpretation correlated with imaging studies, may contribute to its suspected diagnosis.
Its treatment of choice is surgery by means of selective parathyroidectomy with complete cystic inclusion, and extended to the thyroid depending on their degree of involvement, although this technique may experience modifications depending on the level of confidence in preoperative diagnosis.