Bone material strength index as measured by in vivo impact microindentation is normal in subjects with high-energy trauma fractures.

Bone material properties were assessed using impact microindentation in patients with high-energy trauma fractures. Compared to patients with low-energy trauma fractures, bone material strength index was significantly higher in patients with high-energy trauma fractures, and did not differ between patients with osteopenia and those with osteoporosis within each trauma group. INTRODUCTION: Impact microindentation (IMI) is a technique to assess tissue-level properties of bone at the tibia. Bone material strength index (BMSi), measured by IMI, is decreased in patients with low-energy trauma fractures, independently of areal bone mineral density (aBMD), but there is no information about BMSi in patients with high-energy trauma fractures. In the present study, we evaluated tissue-level properties of bone with IMI in patients with high-energy trauma fractures. METHODS: BMSi was measured 3.0 months (IQR 2.0-5.8) after the fracture in 40 patients with high-energy trauma and 40 age- and gender-matched controls with low-energy trauma fractures using the OsteoProbe® device. RESULTS: Mean age of high- and low-energy trauma patients was 57.7 ± 9.1 and 57.2 ± 7.7 years, respectively (p = 0.78). Fracture types were comparable in high- vs low-energy trauma patients. Lumbar spine (LS)-aBMD, but not femoral neck (FN)-aBMD, was higher in high- than in low-energy trauma patients (LS 0.96 ± 0.13 vs 0.89 ± 0.13 g/cm2, p = 0.02; FN 0.75 ± 0.09 vs 0.72 ± 0.09 g/cm2, p = 0.09). BMSi was significantly higher in high- than in low-energy trauma patients (84.4 ± 5.0 vs 78.0 ± 4.6, p = 0.001), also after adjusting for aBMD (p = 0.003). In addition, BMSi did not differ between patients with osteopenia and those with osteoporosis within each trauma group. CONCLUSION: Our data demonstrate that BMSi and LS-aBMD, but not FN-aBMD, are significantly higher in high-energy trauma patients compared to matched controls with similar fractures from low-energy trauma. Further studies of non-osteoporotic patients with high-energy trauma fracture with measurements of BMSi are warranted to determine whether IMI might help in identifying those with reduced bone strength.

Denosumab for the treatment of primary pediatric osteoporosis.

Primary osteoporosis is rare in children and adolescents and its optimal pharmacological management is uncertain. Bisphosphonates are commonly used while denosumab has only been administered to a few children with osteogenesis imperfecta. We studied a treatment-naïve 13.5-year-old boy with severe osteoporosis and multiple vertebral deformities who presented with back pain and difficulty in walking. Causes of secondary osteoporosis were excluded and there were no abnormalities in genes known to cause bone fragility. He was treated with denosumab 60 mg subcutaneously every 3 months for 30 months, and he was pain-free within 6 weeks after the first injection. Lumbar spine BMD and femoral neck BMD increased with treatment by 65.6% and 25.3%, respectively, and deformed vertebrae regained their normal shape; linear growth was not impaired. During the second year of treatment, transient hypercalcemia (maximum 3.09 mmol/l) before the denosumab injection was observed. In conclusion, denosumab was highly effective in this case of primary pediatric osteoporosis, with remarkable clinical and radiological response. Transient hypercalcemia was probably due to amplification of the effect of growth spurt and puberty on bone remodeling by the transient, short-term discontinuation of the drug. Furthermore, our data suggest that mobilization of calcium from treatment-induced sclerotic transverse lines in bone metaphyses may contribute to the development of hypercalcemia.

Treatments of osteoporosis increase bone material strength index in patients with low bone mass.

Effects on bone material properties of two-year antiosteoporotic treatment were assessed using in vivo impact microindentation (IMI) in patients with low bone mineral density (BMD) values. Antiresorptive treatment, in contrast to vitamin D ± calcium treatment alone, induced BMD-independent increases in bone material strength index, measured by IMI, the magnitude of which depended on pretreatment values. INTRODUCTION: Bone material strength index (BMSi), measured by IMI in vivo, is reduced in patients with fragility fractures, but there is no information about changes in values during long-term therapy. In the present study, we assessed changes in BMSi in patients receiving antiosteoporotic treatments for periods longer than 12 months. METHODS: We included treatment-naive patients with low bone mass who had a BMSi measurement with OsteoProbe® at presentation and consented to a repeat measurement after treatment. RESULTS: We studied 54 patients (34 women), median age 58 years, of whom 30 were treated with bisphosphonates or denosumab (treatment group) and 24 with vitamin D ± calcium alone (control group). There were no differences in clinical characteristics between the two groups with the exception of a higher number of previous fragility fractures in the treatment group. Baseline hip BMD and BMSi values were lower in the treatment group. After 23.1 ± 6.6 months, BMSi increased significantly in the treatment group (82.4 ± 4.3 vs 79.3 ± 4.1; p < 0.001), but did not change in the control group (81.5 ± 5.2 vs 82.2 ± 4.1; p = 0.35). Changes in BMSi with antiresorptives were inversely related with baseline values (r = - 0.43; p = 0.02) but not with changes in BMD. Two patients in the control group with large decreases in BMSi values sustained incident fractures. CONCLUSION: In patients at increased fracture risk, antiresorptive treatments induced BMD-independent increases in BMSi values, the magnitude of which depended on pretreatment values.

Bone material strength index as measured by impact microindentation is low in patients with fractures irrespective of fracture site.

We evaluated the relationship between bone material strength index (BMSi) and fragility fractures, including vertebral fractures. Our data showed that BMSi is low in all fracture patients with low bone mass, independently of whether patients sustained a vertebral or a non-vertebral fracture. INTRODUCTION: Impact microindentation (IMI) is a new technique for the measurement of tissue level properties of cortical bone in vivo. Previous studies showed an association between BMSi and non-vertebral fractures, but an association with vertebral fractures is still being debated. The objective of this paper was to evaluate the relationship between BMSi and different types of fragility fractures, including vertebral fractures. METHODS: In this cross-sectional study, we measured BMSi in patients of both sexes with different types of fragility fractures and low bone mass with the IMI method using the Osteoprobe®. Vertebral fractures were diagnosed and graded on lateral spine radiographs. RESULTS: A total of 132 patients were included in the study, of whom 101 patients (65 women) had sustained a low energy fracture and 31 (mean age 57.7 ± 9.9 years) had no history or radiological evidence for a fracture. Of the fracture patients, 53 (mean age 62.8 ± 8.3 years) had only non-vertebral fractures (VF-/Fx+), 34 (mean age 62.8 ± 9.9 years) had vertebral and non-vertebral fractures (VF+/Fx+), and 14 (mean age 64.7 ± 9.3 years) had only vertebral fractures (VF+/Fx-). BMSi values, adjusted for age and BMD, were similar for all three groups of fracture patients (78.9 ± 0.7, 78.3 ± 0.9, and 78.4 ± 1.4, respectively; p = 0.866). BMSi values were not associated with number or severity of vertebral fractures. CONCLUSION: Our data demonstrate that BMSi is low in fracture patients with low bone mass, irrespective of whether they sustained a vertebral fracture or a non-vertebral fracture.

Serum Dickkopf 1 levels in sclerostin deficiency.

CONTEXT: Sclerostin and Dickkopf 1 (DKK1) are antagonists of the canonical Wnt signaling pathway, both binding to the same low-density lipoprotein receptor-related protein 5/6 on osteoblasts, thereby inhibiting bone formation. It is not known whether there is an interaction between sclerostin and DKK1. OBJECTIVE: We examined whether a lack of sclerostin is compensated by increased DKK1 levels. DESIGN, SETTING, AND PATIENTS: We measured DKK1 levels in serum samples of patients and carriers of sclerosteosis (19 patients, 24 carriers) and van Buchem disease (VBD) (13 patients, 22 carriers) and 25 healthy controls. Sclerosteosis and VBD are caused by deficient sclerostin synthesis and are characterized by increased bone formation and hyperostotic phenotypes. MAIN OUTCOME MEASURES: DKK1 levels were compared between patients and carriers, and between patients and healthy controls. We also examined associations between levels of DKK1 and the bone turnover markers procollagen type 1 amino-terminal propeptide and carboxy-terminal cross-linking telopeptide. RESULTS: We found that DKK1 levels were significantly higher in patients with both sclerosteosis (4.28 ng/mL [95% confidence interval (CI), 3.46-5.11 ng/mL]) and VBD (5.28 ng/mL [95% CI, 3.84-6.71 ng/mL]), compared to levels in carriers of the two diseases (sclerosteosis, 2.03 ng/mL [95% CI, 1.78-2.29 ng/mL], P < .001; VBD, 3.47 ng/mL [95% CI, 2.97-3.97 ng/mL], P = 0.017) and to levels in healthy controls (2.77 ng/mL [95% CI, 2.45-3.08 ng/mL]; P = 0.004 and P < .001, respectively). Serum DKK1 levels were positively associated with levels of procollagen type 1 amino-terminal propeptide and carboxy-terminal cross-linking telopeptide in both disorders. CONCLUSIONS: These results suggest that increased DKK1 levels observed in patients with sclerosteosis and VBD represent an adaptive response to the increased bone formation characterizing these diseases, although these increased levels do not compensate for the lack of sclerostin on bone formation.

Long-term treatment of osteoporotic women with bisphosphonates does not impair the response to subsequently administered intravenous pamidronate.

UNLABELLED: We addressed the question whether the response of osteoporotic patients to bisphosphonate treatment is reduced with time. Bisphosphonate-treated women with postmenopausal or glucocorticoid-induced osteoporosis showed adequate and consistent changes of bone markers to subsequently administered intravenous pamidronate. Response of osteoporotic patients to bisphosphonates is not impaired during their long-term administration. INTRODUCTION: Inadequate response to bisphosphonate treatment has been described in patients with Paget's disease of bone but has not been addressed in osteoporosis although treatment failure is a clinically relevant problem. METHODS: Twenty one women with postmenopausal osteoporosis (PMO) aged 68 ± 8.2 years and 14 women with glucocorticoid-induced osteoporosis (GIOP) aged 65 ± 10 years were treated with tri-monthly intravenous infusions of 45 mg of pamidronate for 1 year. All patients had been previously treated with bisphosphonates (alendronate, risedronate, pamidronate) for a mean period of 6.2 years (range, 1.3-14 years). Blood samples were taken for measurement of the bone resorption marker C-terminal crosslinking telopeptide of type I collagen (CTX-I) on days 1 and 4 and of the bone formation marker procollagen type I N propeptide, (P1NP) on day 1 of every tri-monthly treatment course. RESULTS: With each treatment course there was a significant decrease in serum CTX-I on day 4 and an increase to baseline values 3 months after each infusion in both PMO (mean values, day 1: 291.33 ± 160.78 pg/ml vs. day 4: 131 ± 91.7 pg/ml, p < 0.001) and GIOP (day 1: 219.3 ± 114.8 pg/ml vs. day 4: 98.8 ± 51.6 pg/ml, p < 0.001). Serum P1NP remained stable during the whole year of treatment. CONCLUSIONS: Long-term bisphosphonate treatment of women with either PMO or GIOP does not impair the response to subsequently administered intravenous pamidronate suggesting that inadequate response to long-term bisphosphonate treatment is not responsible for treatment failure.

Circulating sclerostin levels are decreased in patients with endogenous hypercortisolism and increase after treatment.

CONTEXT: Increased bone fragility is a frequent complication of hypercortisolism due predominantly to suppression of bone formation. Sclerostin is an osteocyte-produced negative regulator of bone formation, which is up-regulated by glucocorticoids in mice. OBJECTIVE: Our objective was to assess the effect of endogenous hypercortisolism on circulating sclerostin and bone turnover in humans. DESIGN: We measured sclerostin, ß-C-terminal telopeptide, amino-terminal propeptide of type 1 procollagen, and fibroblast growth factor 23 in blood samples of 21 patients with endogenous hypercortisolism and 21 age- and gender-matched controls. In 12 patients, measurements were repeated at various time intervals after successful surgical treatment (transsphenoidal surgery or adrenalectomy). RESULTS: Plasma sclerostin levels were significantly decreased in patients compared with controls (112±49 vs. 207±48 pg/ml, P<0.001). In the 12 patients who were evaluated after surgical treatment, sclerostin levels increased from 121.4±46.5 to 175.8±78.5 pg/ml (P=0.003). These changes in plasma sclerostin levels were accompanied by significant increases in levels of fibroblast growth factor 23 (from 44.2±12.2 to 84.0±58.8 pg/ml, P=0.017) and of the bone turnover markers amino-terminal propeptide of type 1 procollagen (from 31.7±18.2 to 94.2±92.2 ng/ml, P=0.037) and ß-C-terminal telopeptide (from 134.2±44 to 409.2±285 pg/ml, P=0.005). CONCLUSIONS: Contrary to the findings in mice, circulating sclerostin is decreased in patients with chronic endogenous hypercortisolism and increases after treatment. These findings suggest that in humans, chronic exposure to glucocorticoids affects the number or function of osteocytes rather than the production of sclerostin.

A rare cause of facial nerve palsy in children: hyperostosis corticalis generalisata (Van Buchem disease). Three new pediatric cases and a literature review.

Differential diagnosis of facial nerve palsy in children is extensive. We report on three pediatric cases presenting with facial nerve palsy caused by hyperostosis corticalis generalisata (Van Buchem disease). This autosomal recessive disease is characterized by progressive bone overgrowth, with narrowing of the neuroforamina in the skull causing cranial neuropathies. These three new cases of Van Buchem disease are of interest because of exceptionally early presentation of symptoms. Furthermore, this is the first report describing bilateral papilledema in a child with Van Buchem disease. Head computerized tomography (CT) scan revealed thickened calvarium, skull base and mandible in all three children, with narrowed facial nerve canals. Bone mineral density (BMD) was markedly increased at all measured points and biochemical markers of bone formation were significantly elevated. Diagnosis of Van Buchem disease was genetically confirmed. The cases are unique in that these are the first well-documented pediatric cases of Van Buchem disease.

Distinct effects of pioglitazone and metformin on circulating sclerostin and biochemical markers of bone turnover in men with type 2 diabetes mellitus.

OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures and thiazolidinediones (TZDs) increase this risk. TZDs stimulate the expression of sclerostin, a negative regulator of bone formation, in vitro. Abnormal sclerostin production may, therefore, be involved in the pathogenesis of increased bone fragility in patients with T2DM treated with TZDs. METHODS: We measured serum sclerostin, procollagen type 1 amino-terminal propeptide (P1NP), and carboxy-terminal cross-linking telopeptide of type I collagen (CTX) in 71 men with T2DM treated with either pioglitazone (PIO) (30 mg once daily) or metformin (MET) (1000 mg twice daily). Baseline values of sclerostin and P1NP were compared with those of 30 healthy male controls. RESULTS: Compared with healthy controls, patients with T2DM had significantly higher serum sclerostin levels (59.9 vs 45.2 pg/ml, P<0.001) but similar serum P1NP levels (33.6 vs 36.0 ng /ml, P=0.39). After 24 weeks of treatment, serum sclerostin levels increased by 11% in PIO-treated patients and decreased by 1.8% in MET-treated patients (P=0.018). Changes in serum sclerostin were significantly correlated with changes in serum CTX in all patients (r=0.36, P=0.002) and in PIO-treated patients (r=0.39, P=0.020), but not in MET-treated patients (r=0.17, P=0.31). CONCLUSIONS: Men with T2DM have higher serum sclerostin levels than healthy controls, and these levels further increase after treatment with PIO, which is also associated with increased serum CTX. These findings suggest that increased sclerostin production may be involved in the pathogenesis of increased skeletal fragility in patients with T2DM in general and may specifically contribute to the detrimental effect of TZDs on bone.

Interpretation and use of FRAX in clinical practice.

UNLABELLED: The introduction of the WHO FRAX® algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. Its use in fracture risk prediction has strengths, but also limitations of which the clinician should be aware and are the focus of this review INTRODUCTION: The International Osteoporosis Foundation (IOF) and the International Society for Clinical Densitometry (ISCD) appointed a joint Task Force to develop resource documents in order to make recommendations on how to improve FRAX and better inform clinicians who use FRAX. The Task Force met in November 2010 for 3 days to discuss these topics which form the focus of this review. METHODS: This study reviews the resource documents and joint position statements of ISCD and IOF. RESULTS: Details on the clinical risk factors currently used in FRAX are provided, and the reasons for the exclusion of others are provided. Recommendations are made for the development of surrogate models where country-specific FRAX models are not available. CONCLUSIONS: The wish list of clinicians for the modulation of FRAX is large, but in many instances, these wishes cannot presently be fulfilled; however, an explanation and understanding of the reasons may be helpful in translating the information provided by FRAX into clinical practice.

Patients with primary hyperparathyroidism have lower circulating sclerostin levels than euparathyroid controls.

OBJECTIVE: In vitro and in vivo studies in animal models have shown that parathyroid hormone (PTH) inhibits the expression of the SOST gene, which encodes sclerostin, an osteocyte-derived negative regulator of bone formation. We tested the hypothesis that chronic PTH excess decreases circulating sclerostin in humans. DESIGN: We studied 25 patients with elevated serum PTH concentrations due to primary hyperparathyroidism (PHPT) and 49 patients cured from PHPT after successful parathyroidectomy (PTx; euparathyroid controls (EuPTH)). METHODS: We measured plasma PTH and serum sclerostin levels and the serum markers of bone turnover alkaline phosphatase, P1NP, and ß-CTX. RESULTS: As expected by the design of the study, mean plasma PTH was significantly higher (P<0.001) in PHPT patients (15.3 pmol/l; 95% confidence interval (CI): 11.1-19.5) compared with that of EuPTH controls (4.1 pmol/l; 95% CI: 3.6-4.5). PHPT patients had significantly lower serum sclerostin values compared with those in EuPTH subjects (30.5 pg/ml; 95% CI: 26.0-35.1 vs 45.4 pg/ml; 95% CI: 40.5-50.2; P<0.001) and healthy controls (40.0 pg/ml; 95% CI: 37.1-42.9; P=0.01). Plasma PTH concentrations were negatively correlated with serum sclerostin values (r=-0.44; P<0.001). Bone turnover markers were significantly correlated with PTH, but not with sclerostin. CONCLUSION: Patients with PHPT have significantly lower serum sclerostin values compared with PTx controls with normal PTH concentrations. The negative correlation between PTH and sclerostin suggests that SOST is downregulated by PTH in humans.

Sclerostin: current knowledge and future perspectives.

In recent years study of rare human bone disorders has led to the identification of important signaling pathways that regulate bone formation. Such diseases include the bone sclerosing dysplasias sclerosteosis and van Buchem disease, which are due to deficiency of sclerostin, a protein secreted by osteocytes that inhibits bone formation by osteoblasts. The restricted expression pattern of sclerostin in the skeleton and the exclusive bone phenotype of good quality of patients with sclerosteosis and van Buchem disease provide the basis for the design of therapeutics that stimulate bone formation. We review here current knowledge of the regulation of the expression and formation of sclerostin, its mechanism of action, and its potential as a bone-building treatment for patients with osteoporosis.

Ibandronate does not increase risk of atrial fibrillation in analysis of pivotal clinical trials.

OBJECTIVE: To determine the incidence of adverse events or serious adverse events of atrial fibrillation in the pivotal trials of ibandronate and to assess whether increasing dose or duration of exposure had any effect on the incidence of atrial fibrillation. PATIENTS AND METHODS: Pooled data from all four pivotal ibandronate clinical trials were analysed to assess the incidence of atrial fibrillation as an adverse event and serious adverse event with ibandronate vs. placebo. The incidence of atrial fibrillation with ibandronate was also assessed by dose, by annual cumulative exposure (ACE) and by patient age. RESULTS: This analysis included 6830 patients treated with ibandronate and 1924 treated with placebo. The incidence of atrial fibrillation as an adverse event (ibandronate, 0.8% and placebo, 0.9%) and serious adverse event (0.4% for both ibandronate and placebo) was comparable between the ibandronate and placebo groups. There was no increase in the incidence of atrial fibrillation as an adverse event or serious adverse event with increasing oral or intravenous (i.v.) ibandronate dose. No correlation between the incidence of atrial fibrillation as a serious adverse event and ibandronate duration of exposure was observed. Based on various ACE categories, none of the ibandronate regimens evaluated in these trials was associated with an increased incidence of atrial fibrillation. CONCLUSIONS: In this pooled analysis of all four ibandronate pivotal trials, including analysis by ACE, all studied ibandronate regimens, including the licensed doses of 150 mg monthly oral and 3 mg quarterly i.v., were not associated with an increased incidence of atrial fibrillation.

Sclerostin in mineralized matrices and van Buchem disease.

Sclerostin is an inhibitor of bone formation expressed by osteocytes. We hypothesized that sclerostin is expressed by cells of the same origin and also embedded within mineralized matrices. In this study, we analyzed (a) sclerostin expression using immunohistochemistry, (b) whether the genomic defect in individuals with van Buchem disease (VBD) was associated with the absence of sclerostin expression, and (c) whether this was associated with hypercementosis. Sclerostin was expressed by cementocytes in mouse and human teeth and by mineralized hypertrophic chondrocytes in the human growth plate. In individuals with VBD, sclerostin expression was absent or strongly decreased in osteocytes and cementocytes. This was associated with increased bone formation, but no overt changes in cementum thickness. In conclusion, sclerostin is expressed by all 3 terminally differentiated cell types embedded within mineralized matrices: osteocytes, cementocytes, and hypertrophic chondrocytes.

Bisphosphonate dose and incidence of fractures in postmenopausal osteoporosis.

INTRODUCTION: The specific pharmacological properties of bisphosphonates have raised concerns about their long-term effects on skeletal fragility that may be related to the total dose of bisphosphonate given. However, the effect of different doses on the incidence of osteoporotic fractures has not been adequately studied. METHODS: In this retrospective analysis, we investigated the effect of different doses of intravenous pamidronate given at 3-monthly intervals on the incidence of fractures in 92 women with severe postmenopausal osteoporosis. RESULTS: The risk of sustaining a new vertebral fracture on treatment was significantly increased by 32% for every prevalent vertebral fracture (OR: 1.32, CI: 1.05, 1.66; p=0.02). Patients with nonvertebral fractures received a significantly lower dose of pamidronate and their risk for these fractures increased by 25% for every prevalent vertebral fracture at baseline (OR: 1.25, CI: 1.01, 1.53; p=0.03). Patients who had received oral bisphosphonate before intravenous pamidronate had a significantly higher incidence of nonvertebral fractures which, however, did not hold true after adjustment for baseline BMD and prevalent fractures. CONCLUSIONS: In patients with established osteoporosis bone fragility during treatment with intravenous pamidronate is mainly determined by the severity of the disease, assessed by the presence and numbers of prevalent fractures, rather than the dose of the bisphosphonate or the rate of bone turnover.

Synergistic effect of bisphosphonate and docetaxel on the growth of bone metastasis in an animal model of established metastatic bone disease.

Bisphosphonates decrease bone resorption and reduce significantly the rate of skeletal complications in patients with metastatic bone disease. Bisphosphonates have also been shown to exhibit antitumor activity in vitro but in vivo results have been equivocal. In the present study, we investigated the effects of bisphosphonate treatment alone or in combination with the cytostatic docetaxel on the growth of breast cancer cells in bone. Tumor gowth was studied in an athymic nude mice model inoculated with MDA-231-B/luc+ breast cancer cells. Two days after the inoculation, mice were treated with risedronate, zolendronate or docetaxel alone or with a combination of risedronate and docetaxel. Bone destruction and tumor growth were evaluated radiographically, histologically and by whole-body bioiluminescent reporter imaging (BLI). Five week treatment with high doses risedronate or zoledronate (37.5-150 microg/kg, 5 times/week), fully protected the bones from osteolysis, but did not affect tumour growth. Docetaxel (2, 4, and 8 mg/kg, 2 times/week) inhibited tumour growth dose-dependently and after 5 weeks treatment with the highest dose, there was no detectable tumour in bone. The combination of a dose of docetaxel (4 mg/kg) that demonstrated only a minimal effect on tumour growth, with risedronate (150 microg/kg), protected bone integrity and nearly completely inhibited the growth of the cancer cells. Risedronate and docetaxel act synergistically to protect bone and decrease tumour burden in an animal model of established bone metastases from breast cancer cells.

Spine radiographs to improve the identification of women at high risk for fractures.

SUMMARY: In women older than 60 years with clinical risk factors for osteoporosis but without osteoporosis based on bone mineral density (T-score >or= -2.5), a systematic survey with X-rays of the spine identified previously unknown vertebral deformities in 21% of women. INTRODUCTION: This study determines the prevalence of vertebral deformities in elderly women with clinical risk factors for osteoporosis but with BMD values above the threshold for osteoporosis (T-score >or= -2.5). METHODS: Bisphosphonate naïve women older than 60 years attending 35 general practices in the Netherlands with >or=2 clinical risk factors for osteoporosis were invited for BMD measurement (DXA). In women with T-score >or= -2.5 at both spine and the hips, lateral radiographs of the thoracic and lumbar spine were performed. RESULTS: Of 631 women with a DXA measurement, 187 (30%) had osteoporosis (T-score < -2.5 at the spine or the hip). Of the remaining 444 women with T-score >or= -2.5 at both spine and hip, 387 had additional spine radiographs, of whom 80 (21%) had at least one vertebral deformity. CONCLUSION: In elderly women with clinical risk factors for osteoporosis but BMD T-score >or= -2.5, addition of spine radiographs identified vertebral deformities in 21% (95% CI: 17-25). Since these women are at risk of future fractures, antiosteoporotic treatment should be considered.

Changes in bone remodelling and antifracture efficacy of intermittent bisphosphonate therapy: implications from clinical studies with ibandronate.

Bisphosphonates reduce the rate of bone resorption and bone remodelling. Given daily, they decrease the risk of fractures in postmenopausal osteoporosis. When bisphosphonates were given at extended drug-free intervals this antifracture efficacy was generally not seen. This may be due to the different pattern of bone remodelling changes. Data from randomised clinical studies of ibandronate, given orally or intravenously, at different doses and for variable time intervals to women with osteoporosis were examined to explore the relationship between intermittent bisphosphonate therapy, changes in bone resorption and fracture risk. The magnitude of the reduction of the rate of bone resorption at the end of the drug-free interval rather than its fluctuation pattern after bisphosphonate administration determines antifracture efficacy, provided that these fluctuations occur within the premenopausal range. Prolongation of the drug-free interval beyond 2 weeks should be compensated by a dose higher than the cumulative daily dose.

New insights into the role of vitamin D and calcium in osteoporosis management: an expert roundtable discussion.

BACKGROUND: Adequate vitamin D and calcium nutrition play a critical role in the maintenance of musculoskeletal health and are considered the first step in osteoporosis treatment. ROUNDTABLE DISCUSSION: In February 2008 Merck Sharp & Dohme sponsored a 2-day, evidence-based expert panel on the benefits of vitamin D for the patient with osteoporosis and the role of vitamin D in combination with antiresorptive therapy for the management of osteoporosis. One of the primary objectives of the meeting was to review new data on the optimal serum 25-hydroxy vitamin D [25(OH)D] levels. The symposium was attended by 29 researchers and clinicians from Europe and the Middle East. The discussion focused on optimizing vitamin D and calcium nutrition and reducing falls and fractures in osteoporotic patients. CONCLUSIONS: Current evidence and expert opinion suggests that optimal serum 25(OH)D concentrations should be at least 50 nmol/L (20 ng/mL) in all individuals. This implies a population mean close to 75 nmol/L (30 ng/mL). In order to achieve this level, vitamin D intake of at least 20 microg daily is required. There is a wider therapeutic window for vitamin D than previously believed, and doses of 800 IU per day, regardless of sun exposure, season or additional multivitamin use, appear to present little risk of toxicity. Apart from fracture and fall prevention, optimization of vitamin D status may also have additional general health benefits. Based on newly emerging data regarding calcium supplementation, and recommendations for increased vitamin D intake, the current recommendations for calcium intake in postmenopausal women may be unnecessarily high. In addition to vitamin D and calcium, treatment of patients with osteoporosis at high risk of fractures should also include pharmacologic agents with proven vertebral and non-vertebral fracture efficacy.

Changes in bone remodelling and antifracture efficacy of intermittent bisphosphonate therapy: implications from clinical studies with ibandronate.

Bisphosphonates reduce the rate of bone resorption and bone remodelling. Given daily, they decrease the risk of fractures in postmenopausal osteoporosis. When bisphosphonates were given at extended drug-free intervals this antifracture efficacy was generally not seen. This may be due to the different pattern of bone remodelling changes. Data from randomised clinical studies of ibandronate, given orally or intravenously, at different doses and for variable time intervals to women with osteoporosis were examined to explore the relationship between intermittent bisphosphonate therapy, changes in bone resorption and fracture risk. The magnitude of the reduction of the rate of bone resorption at the end of the drug-free interval rather than its fluctuation pattern after bisphosphonate administration determines antifracture efficacy, provided that these fluctuations occur within the premenopausal range. Prolongation of the drug-free interval beyond 2 weeks should be compensated by a dose higher than the cumulative daily dose.