George Trovas

Type 2 diabetes mellitus and fracture risk

Increased fracture risk, traditionally associated with type 1 diabetes, has lately been of great concern in patients with type 2 diabetes. A variable increase in fracture risk has been reported, ranging from 20% to 3-fold, depending on skeletal site, diabetes duration and study design. Longer disease duration, the presence of diabetic complications, inadequate glycemic control, insulin use and increased risk for falls are all reported to increase fracture risk. Patients with type 2 diabetes display a unique skeletal phenotype with either normal or more frequently increased, bone mineral density and impaired structural and geometric properties. Recently, alterations in bone material properties seem to be the predominant defect leading to increased bone fragility. Accumulation of advanced glycation end-products and changes in collagen cross-linking along with suppression of bone turnover seem to be significant factors impairing bone strength. FRAX score has been reported to underestimate fracture risk and lumbar spine BMD is inadequate in predicting vertebral fractures. Anti-diabetic medications, apart from thiazolidinediones, appear to be safe for the skeleton, although more data are needed. Optimal strategies to reduce skeletal fragility in type 2 diabetic patients are yet to be determined.

The use of bisphosphonates in women prior to or during pregnancy and lactation.

OBJECTIVE: The unique pharmacokinetics of bisphosphonates (BPs) in conjunction with their use by an increasing number of women at reproductive age has raised serious concerns about their safety during pregnancy and lactation. Bisphosphonates cross the placenta. Animal studies have shown adverse effects on both the fetus and the mother, mostly at doses much higher than those commonly used in humans. Protracted parturition, maternal mortality, embryolethality, severe general underdevelopment and marked skeletal retardation of the fetuses (increased amount of diaphyseal bone trabeculae, decreased diaphyseal length), small fetal weight and abnormal tooth growth have been observed. DESIGN: We conducted a thorough research of the literature in order to identify human studies concerning this issue. RESULTS: We identified a total of 78 cases involving fetuses whose mothers had been exposed to BPs before conception or during pregnancy, along with 7 cases of BPs exposure prior to or during lactation. The vast majority of mothers and infants did not demonstrate serious adverse effects. However, there were cases of shortened gestational age, low neonatal birth weight and transient hypocalcaemia of the newborns, while the very few reported cases of spontaneous abortions and congenital anomalies probably resulted from maternal underlying diseases and concomitant medication. CONCLUSION: The administration of bisphosphonates in pregnancy should be assessed in view of their potential hazardous effects on both mother and fetus. In cases of absolute or relative indications of BPs prior to pregnancy, close observation of the mother and the infant, especially during the first two weeks of life, is imperative for the successful outcome of pregnancy.

Case report: Teriparatide treatment in a case of severe pregnancy -and lactation- associated osteoporosis.

OBJECTIVEPregnancy- and lactation-associated osteoporosis (PLO) is an uncommon disease. The majority of cases are seen in the third trimester or early post-partum in primagravid women and the prominent clinical feature of PLO is severe and prolonged back pain and height loss. The prevalence and aetiology of this disorder are as yet unclear and there are no guidelines for its treatment.CASE REPORTWe report the outcomes of teriparatide (TRP) treatment in a woman suffering from severe PLO with 6 vertebral fragility fractures, severe back pain and very low BMD.RESULTSThirteen months after the initiation of therapy, the patient was almost free of back pain. There was no new clinical vertebral fracture. Her laboratory tests were all normal. BMD increased by 24.4% at the lumbar spine, 9.9% and 4.6% at the left and the right total hip and 12.6% and 7.8% at the left and right femur neck, respectively.CONCLUSIONTRP treatment simultaneously with weaning and calcium and vitamin D supplementation seems to considerably increase BMD, improve severe back pain and quality of life and prevent further occurrence of vertebral fractures, making TRP a helpful tool in restoring bone strength in PLO patients.

Changes in biochemical indices of bone metabolism in post-menopausal women following a dietary intervention with fortified dairy products.

BACKGROUND In southern Europe, calcium supplementation alone is a common practice for osteoporosis prevention. The present study aimed to examine whether calcium supplementation alone could be as effective in achieving favourable changes on bone metabolism indices of Greek post-menopausal women as a holistic dietary approach combining consumption of dairy products fortified with calcium and vitamin D(3) and nutrition counselling sessions for five winter months. METHODS A sample of 101 post-menopausal women was randomised to a dairy intervention group (IG: n = 39), receiving approximately 1200 mg of calcium and 7.5 microg of vitamin D(3) per day via fortified dairy products and attending biweekly nutrition counselling sessions; a calcium-supplemented group (SG: n = 26) receiving a total of 1200 mg calcium per day; and a control group (CG: n = 36). RESULTS Regarding insulin-like growth factor (IGF)-I, a higher increase was observed for the IG compared to the changes in the CG and the SG (P = 0.049). Regarding serum parathyroid hormone (PTH) levels, the increase observed in the CG was higher than the changes observed in the other two groups but the differences were of marginal significance (P = 0.055). No significant differences were observed among groups regarding the changes in serum osteocalcin and type I collagen cross-linked C-telopeptide levels. CONCLUSIONS The application of a holistic intervention approach combining nutrition counselling and consumption of fortified dairy products for five winter months induced some more favourable changes in IGF-I and PTH levels compared to calcium supplementation alone. Intervention periods longer than 5 months might be required to achieve significant differences among groups for bone remodelling biomarkers as well.

Severe osteoporosis and mutation in NOTCH2 gene in a woman with Hajdu-Cheney syndrome

Hajdu-Cheney syndrome (HCS) is a rare genetic disorder characterised by acro-osteolysis, skull deformation and generalised osteoporosis. Recently, truncating mutations in the last exon of NOTCH2, a protein-coding gene, were found to be responsible. We present the case of a young woman with HCS in whom clinical and radiologic diagnosis was confirmed with DNA tests.

The role of vitamin D receptor gene polymorphisms in the bone mineral density of Greek postmenopausal women with low calcium intake.

The aim of this study was to investigate the effect of common vitamin D receptor (VDR) gene polymorphisms on the bone mineral density (BMD) of Greek postmenopausal women. Healthy postmenopausal women (n=578) were recruited for the study. The BMD of the lumbar spine and hip was measured using dual-energy X-ray absorptiometry with the Lunar DPX-MD device. Assessment of dietary calcium intake was performed with multiple 24-h recalls. Genotyping was performed for the BsmI, TaqI and Cdx-2 polymorphisms of the VDR gene. The selected polymorphisms were not associated with BMD, osteoporosis or osteoporotic fractures. Stratification by calcium intake revealed that in the low calcium intake group (<680 mg/day), all polymorphisms were associated with the BMD of the lumbar spine (P<.05). After adjustment for potential covariates, BsmI and TaqI polymorphisms were associated with the presence of osteoporosis (P<.05), while the presence of the minor A allele of Cdx-2 polymorphism was associated with a lower spine BMD (P=.025). In the higher calcium intake group (>680 mg/day), no significant differences were observed within the genotypes for all polymorphisms. The VDR gene is shown to affect BMD in women with low calcium intake, while its effect is masked in women with higher calcium intake. This result underlines the significance of adequate calcium intake in postmenopausal women, given that it exerts a positive effect on BMD even in the presence of negative genetic predisposition.

Low-Density Lipoprotein Receptor-Related Protein 5 Polymorphisms Are Associated with Bone Mineral Density in Greek Postmenopausal Women: An Interaction with Calcium Intake

The low-density lipoprotein receptor-related protein 5 (LRP5) has been shown to play a significant role in bone biology. This study aimed to assess the association of four common polymorphisms of the LRP5 gene with bone mineral density (BMD) and possible genexcalcium intake interactions in Greek postmenopausal women. For this observational cross-sectional association study, healthy postmenopausal women (N=578) were recruited (between December 2006 and January 2008) and genotyped for four polymorphisms (rs1784235, rs491347, rs4988321, and rs4988330) in the LRP5 gene. Measurements of BMD were performed and detailed medical, dietary, and anthropometric data were recorded. Student t tests and multiple linear regression models were applied after controlling for potential covariates (ie, age, weight, height, and calcium intake). None of the polymorphisms was associated with the presence of osteoporosis, fractures, and hip BMD. All polymorphisms were associated with unadjusted spine BMD, with the exception of rs4988330. Only rs4988321 was associated with adjusted spine BMD, where the presence of the A allele was associated with significantly lower spine BMD compared with the GG genotype (P=0.002). An interaction of the rs4988321 polymorphism with calcium intake (P=0.016) was found. The carriers of the A allele demonstrated significantly lower spine BMD compared to GG homozygotes (P=0.001) only in the lowest calcium intake group (<680 mg/day), whereas in the highest calcium intake group no differences were found in BMD between genotypes. These findings demonstrate that both rs4988321 polymorphism and its interaction with calcium intake are associated with BMD, whereas higher calcium intake was shown to decrease the negative effect of this polymorphism on BMD.

Quantitative Ultrasound of the Calcaneus in Greek Women: Normative Data are Different From the Manufacturer's Normal Range

Quantitative ultrasound (QUS) is considered a useful method in evaluating bone status. The aim of the present study was to establish the reference data for the QUS measurements of the calcaneus in a Greek population. We measured a QUS parameter, stiffness index (SI), at the right calcaneus in 1500 women using the Achilles express Ultrasonometer (GE Lunar, Madison, WI). Participants were divided into 7 groups according to their age with a 10-yr span in each group. A progressive decline was found in the SI values after the age of 39 yr in the current study. When the SI values were compared between the age groups, high statistically significant differences were obvious, especially between 20-29 and 50- to 59-yr age groups and 60-69 and 70- to 79-yr age groups (p < 0.0005). Additionally, in the Greek normal range (GNR), the SI values of those aged 60-69 and 70-79 yr were significantly higher (81.84+/-16.14 and 77.45+/-17.65, respectively) than those in the manufacturers normal range (MNR; 75.84+/-16.14 and 69.10+/-17.65, p < 0.005, respectively). Using the manufacturers values, significantly fewer women were classified as normal (48% vs 67.3%), although those with T-score < or =-2.5 were more (15.7%) compared with our Greek value (1.5%), and classification of subjects into risk-of-fracture categories was significantly different (kappa: 0.459, 66.2%, p < 0.0005). Multiple regression analysis showed that weight was the most significant predictor for SI in the age groups 30-39 (beta = 0.280, p < 0.05), 40-49, 60-69, and 70-79 yr (beta = 0.185, p < 0.005; beta = 0.329, p < 0.0005; beta = 0.494, p<0.0005, respectively). Using conventional categories of risk, we report a different classification of our subjects from those proposed by the manufacturer, supporting the concept that data specific to the Greek population are necessary.

A review on osteoporosis in men

ConclusionsOsteoporosis and fragility fractures in men comprise a major public health issue due to the severity of their consequences and the economic burden they pose. Health providers should be aware of the limited symptoms and signs of the disease as well as of its possible underlying causes in order to decide on treatment promptly. A fragility fracture is often the first manifestation of the disease and also an alert for further investigation, as a second fracture often follows. Diagnosis is facilitated by a variety of exams, but the decision for treatment is, in many cases, based on the medical practitioner’s estimation of fracture risk. Prevention and treatment follow the same principles as in osteoporosis in women, although there are fewer medication alternatives available. Identification of the aetiology of primary male osteoporosis will provide more diagnostic and treatment options.