Effect of Calcium and Vitamin D Supplementation With and Without Collagen Peptides on Volumetric and Areal Bone Mineral Density, Bone Geometry and Bone Turnover in Postmenopausal Women With Osteopenia.

Collagen peptides (CPs) have been shown to potentially have a role as a treatment option in osteopenia. In the present randomized prospective study, we examined the effect of calcium, vitamin D with and without CPs supplementation on changes in volumetric bone mineral density (vBMD) and bone geometry assessed by peripheral quantitative computed tomography at the tibia, areal bone mineral density (aBMD) assessed by dual-energy X-ray absorptiometry at the lumbar spine and the hip and bone turnover markers over 12-mo. Fifty-one postmenopausal women with osteopenia were allocated to Group A who received orally 5 g CPs, 500 mg calcium and 400 IU vitamin D3 and Group B who received the same dose of calcium and vitamin D3 per day. The primary endpoint was the change of trabecular bone mineral content (BMC) and vBMD after 12-mo supplementation in Groups A and B. At the trabecular site (4% of the tibia length), Group A had a significant increase of total BMC by 1.96 ± 2.41% and cross-sectional area by 2.58 ± 3.91%, trabecular BMC by 5.24 ± 6.48%, cross-sectional area by 2.58 ± 3.91% and vBMD by 2.54 ± 3.43% and a higher % change of these parameters at 12 mo in comparison to Group B (p < 0.01, p = 0.04, p < 0.01, p = 0.04, p = 0.02, respectively). At the cortical site (38% of the tibia length), total and cortical vBMD increased by 1.01 ± 2.57% and 0.67 ± 1.71%. Furthermore, the mean aBMD at the spine was higher (p = 0.01), while bone markers decreased in Group A compared to Group B. The present study shows improvement of trabecular and cortical parameters as assessed by peripheral quantitative computed tomography at the tibia, prevention of aBMD decline and decrease of bone turnover after 12-mo supplementation with calcium, vitamin D with CPs.

Does Vitamin D affects changes in volumetric bone mineral density and architecture in postmenopausal women after conservatively treated distal radius fractures?

OBJECTIVE: We examined the role of vitamin D on volumetric bone mineral density (vBMD) and architecture during the first week's post-fracture in postmenopausal women (PMW) with distal radial fractures (DRF) treated conservatively using peripheral Quantitative Computed Tomography (pQCT). METHODS: Patients were classified into 2 groups according to initial median 25(OH)D level; Group A (25(OH)D ≥15 ng/ml) and group B (25(OH)D <15 ng/ml). All patients were followed for 12 weeks at three visits: baseline, 6 weeks and 12 weeks post fracture. pQCT was performed at baseline in fractured and contralateral non-fractured radius and at 6th and 12th week on the fractured side. RESULTS: 39 patients completed the protocol. Mean 25(OH)D levels were 15.60±7.35 ng/ml (3.5-41.7). Trabecular (trab) bone mineral content (BMC) and trabvBMD increased at 6 wk. vs. baseline (p<0.001). Cortical BMC, cortvBMD and cross- sectional area (CSA) progressively decreased (p<0.001) during the 12 weeks. There was no interaction between baseline 25(OH)D levels and changes in trabecular and cortical BMC, vBMD and CSA. Advanced age and higher CTX and P1NP were associated with higher cortical bone loss. CONCLUSION: Vitamin D deficiency does not affect the early architectural changes after a DRF. Advanced age and higher bone remodeling were associated with higher cortical bone loss, probably related to immobilization and independent of vitamin D levels.

Effect of calcium and vitamin D supplementation with and without collagen peptides on bone turnover in postmenopausal women with osteopenia.

OBJECTIVES: Collagen peptides (CPs) seem to exert beneficial effects on bone and may have a role as a treatment option. In the present randomized prospective study, we aimed to examine the efficacy, as expressed by changes in P1NP and CTX, and the tolerability of 3-month supplementation of calcium, vitamin D with or without bioactive CPs in postmenopausal women with osteopenia. METHODS: Fifty-one female, postmenopausal women with osteopenia were allocated to two groups: Group A received a sachet containing 5 g CPs, 3.6 g calcium lactate (equivalent to 500 mg of elemental calcium) and 400 IU vitamin D3 and group B received a chewable tablet containing 1.25 g calcium carbonate (equivalent to 500 mg of elemental calcium) and 400 IU vitamin D3 daily. RESULTS: In group A, the P1NP levels significantly decreased by 13.1% (p<0.001) and CTX levels decreased by 11.4% (p=0.058) within 3 months of supplementation. In group B, P1NP and CTX did not change. Group A presented better compliance in comparison to group B and no adverse events contrary to group B. CONCLUSIONS: These findings may reflect the reduction of the increased bone turnover in postmenopausal women with the use of calcium, vitamin D and CPs supplements. The addition of CPs in a calcium and vitamin D supplement may enhance its already known positive effect on bone metabolism. Clinical Trial ID: NCT03999775.

Effect of parathyroidectomy versus risedronate on volumetric bone mineral density and bone geometry at the tibia in postmenopausal women with primary hyperparathyroidism.

The objective of the study was to evaluate the effect of parathyroidectomy (PTX) versus 35 mg once-weekly (ow) risedronate administration on volumetric bone mineral density (vBMD) and bone geometry at the tibia in postmenopausal women with primary hyperparathyroidism (PHPT). Our open-label prospective observational study included 32 postmenopausal women with PHPT as the study group: 16 underwent PTX and 16 were treated with 35 mg ow risedronate for 2 years. We assessed areal BMD (aBMD) by DXA, and vBMD and bone mineral content (BMC) (cortical and trabecular area) by peripheral quantitative computed tomography (pQCT) at the tibia at baseline and at 2 years. Risedronate did not result in any significant change on vBMD and structural pQCT indices. PTX resulted in significant increase in trabecular (trab) BMC (6.44 %) and vBMD (4.64 %), with percent increase being significantly higher than risedronate (p < 0.05). At cortical sites, there was no significant change following PTX. However, the percent change in cortical (cort) vBMD was higher following PTX versus risedronate (0.39 % vs. -0.26 %, p < 0.05). In conclusion, in postmenopausal women with PHPT, PTX is superior to ow risedronate, in terms of improvement of trabecular mineralization and vBMD at the tibia, whereas the effect at cortical sites is less pronounced.

Sarcopenic Obesity in Individuals With Neurodisabilities: The SarcObeNDS Study.

Introduction: Patients with neurodisabilities (NDS) are prone to alterations in body composition. Sarcopenic obesity (SO) is a condition characterized by increased adipose tissue accompanied by sarcopenia. The aim of this study was to investigate the prevalence of SO in patients with NDS, including stroke, spinal cord, and traumatic brain injuries. Methods: The study Sarcopenic Obesity in NeuroDisabled Subjects (acronym: SarcObeNDS) was a cross-sectional study of hospitalized patients (n = 82) and healthy controls (n = 32) with a mean age of 60.00 ± 14.22 years old. SO and sarcopenia were assessed through total body fat % (TBF %), fat mass index (fat mass to height2: FMI = FM/h2; kg/m2), and skeletal muscle index (appendicular skeletal muscle to height2: SMI = ASM/h2; kg/m2) via full-body dual-energy X-ray absorptiometry (DXA). This study was registered in the international database ClinicalTrials.gov with the unique identification number NCT03863379. Results: A statistically significant difference was found in SMI (7.18 ± 0.95 vs. 6.00 ± 1.13 kg/m2, p < 0.001) between controls and patients with NDS. No statistical significance was found for TBF (p = 0.783) and FMI (p = 0.143) between groups. The results remained the same after controlling the results for gender and BMI. A strong positive correlation was demonstrated between BMI and TBF for the total population (r = 0.616, p < 0.001), the control group (r = 0.616, p < 0.001), and patients with NDS (r = 0.728, p < 0.001). Conclusion: In summary, we observed significantly lower BMI and SMI scores in both genders compared to healthy controls. At the clinical level, a timely diagnosis and rapid treatment of sarcopenia and/or obesity in this population may prevent further metabolic repercussions accompanied by higher functional decline and lower quality of life.

Vitamin D and COVID-19.

Epidemiological data report that several countries with a high prevalence of hypovitaminosis D may have increased susceptibility to complications and mortality due to COVID-19 infection. These reports, however, have limitations given that they derive from observational studies. Nevertheless, while awaiting more robust data, clinicians should treat patients with vitamin D deficiency irrespective of whether or not it has a link with respiratory infections.

Cardiovascular Risk in Patients with Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is one of the most common endocrine disorders characterized by parathyroid hormone (PTH)-dependent hypercalcemia. Cardinal features include low trauma fractures, nephrolithiasis, and chronic kidney disease. Several experimental studies established that parathyroid hormone exerts actions on the cardiovascular (CV) system, including vasodilatation and positive inotropic and chronotropic effects. Observational studies, especially in severe cases, report a higher prevalence of hypertension, diabetes mellitus, lipid abnormalities, endothelial dysfunction, arrhythmias, and left ventricular hypertrophy in patients with PHPT, while the risk of CV events seems to be increased in severe cases. However, the effect of surgery is inconsistent on CV abnormalities and, more importantly, on CV disease (CVD) events, especially in mild cases. In the current review, we describe the available evidence linking PHPT and CVD, as well as the effect of surgical management and pharmacological treatment on CVD manifestations in patients with PHPT. Based on the current evidence, CVD is not considered an indication for surgery.

Dietary Patterns of Greek Adults and Their Associations with Serum Vitamin D Levels and Heel Quantitative Ultrasound Parameters for Bone Health.

The aim of this study is to investigate the dietary patterns which indicate the nutritional habits of Greek adults and their effects on serum 25(OH)D levels and quantitative ultrasound (QUS) parameters for bone health. This study is part of OSTEOS, an observational cross-sectional study. In total, 741 adults from rural and urban areas throughout Greece were recruited. A validated food frequency questionnaire (FFQ) was used for assessment of the population's dietary habits. Serum 25(OH)D was measured by enzyme immunoassay; QUS parameters were assessed with an Achilles device. Principal component analysis (PCA) was carried out for dietary pattern determination, and univariate analysis of variance was used for the assessment of 25(OH)D, broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) determinants. Six dietary patterns explain 52.2% of the variability of Greek adults' nutritional habits. The 'vegetables-fruit' dietary pattern explains the biggest rate of variability. Determinants of serum 25(OH)D are body mass index (BMI), elderly status, summer sun exposure, organized physical activity, a 'healthy' pattern in winter months, and adherence to a 'sweet' pattern. Determinants of QUS parameters are age, BMI, sedentary time, organized physical activity participation, and adherence to a 'healthy' pattern.

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 manufacturer's normal range (MNR; 75.84+/-16.14 and 69.10+/-17.65, p < 0.005, respectively). Using the manufacturer's 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.

Hypercalcitoninaemia in pseudohypo-parathyroidism type 1A and type 1B.

Pseudohypoparathyroidism (PHP) is a heterogeneous group of rare endocrine disorders characterised by normal renal function and renal resistance to the action of the parathyroid hormone. Type 1A (PHP1A), which is the most common variant, also include developmental and skeletal defects named as Albright hereditary osteodystrophy (AHO). We present two cases, a 54- and a 33-year-old male diagnosed with PHP who were referred to us for persistently high levels of serum calcitonin. AHO and multinodular goitre were present in the 54-year-old male, while the second patient was free of skeletal deformities and his thyroid gland was of normal size and without nodular appearance. We performed GNAS molecular analysis (methylation status and copy number analysis by MS-MLPA) in genomic DNA samples for both patients. The analysis revealed a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1, in the patient with the clinical diagnosis of PHP1A. This amino acid change appears to be in accordance with the clinical diagnosis of the patient. The genomic DNA analysis of the second patient revealed the presence of the recurrent 3-kb deletion affecting the imprinting control region localised in the STX16 region associated with the loss of methylation (LOM) at the GNAS A/B differentially methylated region and consistent with the diagnosis of an autosomal dominant form of PHP type 1B (PHP1B). In conclusion, hypercalcitoninaemia may be encountered in PHP1A and PHP1B even in the absence of thyroid pathology. Learning points: We describe a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1 as the cause of PHP1A. Hypercalcitoninaemia in PHP1A is considered an associated resistance to calcitonin, as suggested by the generalised impairment of Gsα-mediated hormone signalling. GNAS methylation defects, as in type PHP1B, without thyroid pathology can also present with hypercalcitoninaemia.

The 2018 Guidelines for the diagnosis and treatment of osteoporosis in Greece.

We report the updated guidelines for the management of osteoporosis in Greece, which include guidance on fracture risk assessment, diagnosis-pharmacological treatment-follow-up of osteoporosis based on updated information, and national evidence from Greek clinical practice and the healthcare setting. PURPOSE: The purpose of this report was to update the Guidelines for the Management of Osteoporosis in Greece that was published in 2011. METHODS: In line with the GRADE system, the working group initially defined the main clinical questions that should be addressed when dealing with the diagnosis and management of osteoporosis in clinical practice in Greece. Following a literature review and discussion on the experience gained from the implementation of the 2011 Guidelines transmitted through the national electronic prescription network, the Hellenic Society for the Study of Bone Metabolism (HSSBM) uploaded an initial draft for an open dialogue with the relevant registered medical societies and associations on the electronic platform of the Greek Ministry of Health. After revisions, the Central Health Council approved the final document. RESULTS: The 2018 Guidelines provide comprehensive recommendations on the issues of the timing of fracture risk evaluation and dual-energy X-ray absorptiometry (DXA) measurement, interpretation of the DXA results, the diagnostic work-up for osteoporosis, the timing as well as the suggested medications for osteoporosis treatment, and the follow-up methodology employed during osteoporosis treatment. CONCLUSIONS: These updated guidelines were designed to offer valid guidance on fracture risk assessment, diagnosis-pharmacological treatment-follow-up of osteoporosis based on updated information and national evidence from clinical practice and the healthcare setting. Clinical judgment is essential in the management of every individual patient for the purpose of achieving the optimal outcome in the safest possible way.

Serum 25-hydroxyvitamin D status, quantitative ultrasound parameters, and their determinants in Greek population.

Vitamin D deficiency and quantitative ultrasound measurements are associated with bone fragility. We assessed these parameters and their correlates. 87.7% of the population has vitamin D inadequacy and this correlated with lifestyle factors. These results contribute to epidemiological data needed for population guidelines for bone health. PURPOSE: Vitamin D deficiency and quantitative ultrasound (QUS) parameters are among the most important clinical risk factors of bone fragility. Few data are available for Greek population. The aim of the study was to evaluate the serum 25-hydroxyvitamin D [25(OH)D] level and their determinants, as well as QUS parameters in Greek population. METHODS: OSTEOS is an observational cross-sectional study conducted from June 2010 to July 2012. Nine hundred seventy adults were recruited from rural and urban areas throughout Greece and completed the appropriate questionnaire. Serum 25(OH)D measured by enzyme immunoassay, QUS parameters, broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI), was assessed with an Achilles device. Univariate Analysis of Variance was used for the assessment of serum 25(OH)D determinants. RESULTS: Mean serum 25(OH)D of the total population was 20,00 ± 8,00 ng/mL. Females had lower levels than males. The negative determinants of serum 25(OH)D in the total population were the female sex and the winter-spring season of sampling while age proved negative association solely in obese subjects. Positive determinants of vitamin D status were summer sun exposure and organized physical activity as expected. Urban had lower SOS and SI than rural residents. Individuals with 25(OH)D ≥ 20 ng/mL had higher SOS than those with 25(OH)D < 20 ng/mL. BUA, SOS, and SI are positively correlated with organized physical activity and negatively with PTH. CONCLUSIONS: This study reports that vitamin D deficiency is highly prevalent among healthy Greek men and women, demonstrates the multifactorial causation of 25(OH)D levels, and points out that further research is required to determine more factors related to vitamin D status and bone health.

Changes in biochemical indexes of bone metabolism and bone mineral density after a 12-mo dietary intervention program: the Postmenopausal Health Study.

BACKGROUND: In southern Europe, calcium supplementation alone is a common practice for osteoporosis prevention. OBJECTIVE: We examined whether calcium supplementation could be as effective in achieving favorable bone mass changes in postmenopausal women as is a holistic dietary approach including dairy products fortified with calcium and vitamin D3. DESIGN: A sample of 101 postmenopausal women were randomly assigned to a dairy intervention group (n = 39) who received daily approximately 1200 mg Ca and 7.5 microg vitamin D3 via fortified dairy products and attended biweekly nutrition education sessions; a calcium-supplemented group (n = 26) who received a total of 1200 mg Ca/d; and a control group (n = 36). RESULTS: The increases observed in serum concentrations of insulin-like growth factor I were greater in the dairy intervention group than in the 2 other groups, especially during the first 5 mo of intervention (P = 0.034). The decreases and increases observed during 5 and 12 mo, respectively, in serum 25-hydroxyvitamin D3 were significant in all groups (P = 0.050). Serum parathyroid hormone increased only in the control group, and serum type 1 collagen cross-linked C-telopeptide decreased only in the dairy intervention group during both 5 and 12 mo of intervention (P = 0.035 and 0.047, respectively). The dairy intervention group had greater improvements in pelvis (P = 0.040), total spine (P = 0.001), and total-body (P = 0.001) bone mineral density than did the other 2 groups. CONCLUSION: The application of a holistic intervention approach combining nutrition education and consumption of fortified dairy products for 12 mo can induce more favorable changes in biochemical indexes of bone metabolism and bone mineral density than can calcium supplementation alone.

Quantitative ultrasound is better correlated with bone mineral density and biochemical bone markers in elderly women.

The association between quantitative ultrasound (QUS) and bone turnover in postmenopausal women of different ages is an area of continuous investigation. The aim of this study was to investigate the relationship of ultrasound parameters [broadband ultrasound attenuation (BUA) and speed of sound (SOS)] to bone mineral density (BMD) and biochemical markers of bone turnover in three age groups of postmenopausal women. One hundred and twenty-three postmenopausal Caucasian women were divided into three groups according to their age: group A, range 44-54 years, mean age (+/-SD) 48.3 +/- 2.3; group B, range 55-65 years, mean age 59.4 +/- 2.1; and group C, range 66-77 years, mean age 68.2 +/- 3.1. Ultrasound parameters were measured by the DTU-one imaging ultrasonometer in the calcaneus. BMD was assessed by dual-energy X-ray absorptiometry (DEXA) at the lumbar spine, femoral neck, and trochanter. Bone turnover was assessed by serum bone-specific alkaline phosphatase (BAP), urinary excretion of free deoxypyridinoline, N-telopeptides (NTX), and C-telopeptide breakdown products of type I collagen (CTX). QUS and BMD were significantly correlated in all sites, except hip BMD in group A. The most significant correlation was observed between BUA and femoral neck BMD in group C (r = 0.626, p < 0.01). BUA correlated significantly with BAP, NTX, and CTX (r = -0.434, -0.511, -0.478, respectively; p < 0.01), and SOS with BAP and NTX (r = -0.351 and -0.356, respectively; p < 0.05) only in group C. In groups A and B, ultrasound parameters did not correlate significantly to biochemical markers. Ultrasound parameters were better correlated to hip BMD and to biochemical markers of bone turnover in elderly postmenopausal women. These ultrasound measurements could be used as a screening test for bone status, either in nonambulatory third aged women or in those living in rural areas where attending medical centers with DEXA equipment and biochemical laboratories is difficult.

Effect of Calcitriol on FGF23 Level in Healthy Adults and its Dependence on Phosphate Level.

AIM: To evaluate the short-term effects of calcitriol and sevelamer hydrochloride on fibroblast growth factor-23 (FGF23) in humans and to determine whether the effect is direct or indirect through calcitriol-induced increased absorption of phosphorus from the intestine. PATIENTS AND METHODS: A total of 15 healthy individuals were tested at three time points and stages, for 24 h and at 1-week intervals. During each stage, blood samples were taken at three time points (0, 8 and 24 h); baseline stage: under no intervention; second stage, while receiving 0.5 µg calcitriol orally twice daily; and at the third stage, while receiving 0.5 µg calcitriol orally twice daily and sevelamer hydrochloride during meals. The changes in FGF23, parathyroid hormone, calcitriol, Ca, and phosphorus were determined. RESULTS: During calcitriol administration, the FGF23 level changed significantly (p=0.008), with the level at 24 h levels being significantly higher than at 8 h (8.8 pg/ml vs. 13.0 pg/ml, p=0.036). There was a statistically significant difference in the percentage change, among the three stages, at time 8 to 24 h and 0 to 24 h for FGF23 (p=0.014 and p=0.015, respectively), with significant differences between baseline vs. calcitriol for 8 to 24 h FGF23 change (-9.23% vs. 26.98%, p=0.003) and a trend between baseline vs. calcitriol (p=0.061) and calcitriol plus sevelamer (p=0.069) for 0 to 24 h FGF23 change. CONCLUSION: Administration of calcitriol to healthy individuals increases the circulating level of FGF23 within 24 h. Combined calcitriol and sevelamer administration restrains the increase of FGF23, suggesting that calcitriol-induced increased absorption of phosphate from the intestine might also be involved in the increase of FGF23.

Effect of primary hyperparathyroidism on volumetric bone mineral density and bone geometry assessed by peripheral quantitative computed tomography in postmenopausal women.

CONTEXT: Primary hyperparathyroidism (PH) is characterized by inappropriate PTH elevation with or without hypercalcemia. Bone disease involves catabolic action at cortical sites, whereas cancellous sites and geometry might be relatively preserved. OBJECTIVE: Our objective was to examine the effect of PH on quantitative and qualitative bone characteristics using peripheral quantitative computed tomography at the tibia in postmenopausal women with PH and healthy controls. DESIGN AND SETTING: We conducted a cross-sectional study at a tertiary referral center. PATIENTS: Fifty-two postmenopausal women with PH and 56 healthy controls, comparable for age and anthropometric measures, participated. INTERVENTION: There was no intervention. MAIN OUTCOME MEASURE: We assessed volumetric bone mineral density (vBMD), bone mineral content (BMC), cortical thickness, cortical and trabecular area, peri- and endosteal circumference, and polar stress strength index assessed by peripheral quantitative computed tomography of the left tibia at 4% (cancellous), 14% (transition zone), and 38% (cortical) from the distal end. RESULTS: At 4%, there was a significant decrease of trabecular BMC and vBMD (P < 0.001), effect particularly evident in hypercalcemic patients, whereas trabecular area was comparable. At 38%, cortical BMC (P < 0.01), vBMD (P < 0.01), area (P < 0.05), and thickness (P < 0.001) were reduced in the PH group, particularly in hypercalcemic patients. Endosteal circumference increased (P < 0.001), whereas periosteal circumference was comparable, indicating cancellization of cortical bone. At 14%, polar stress strength index was significantly decreased (P < 0.01) in hypercalcemic patients, indicating impairment of bone mechanical properties. CONCLUSIONS: Normocalcemic PH is characterized by catabolic actions at both cortical and cancellous sites (38 and 4%, respectively), an effect accentuated in hypercalcemic patients. Cortical geometric properties are adversely affected even in normocalcemic patients, whereas trabecular properties are generally preserved.

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.

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.