Indications to teriparatide treatment in patients with osteoporosis.

To prevent osteoporotic fracture occurrence, a variety of treatment regimens with different mechanisms of action is available. The antiresorptive bisphosphonate drugs are currently the most commonly prescribed agents in the management of patients with osteoporosis. The recombinant amino-terminal fragment of human parathyroid hormone (Teriparatide) is a bone anabolic agent which reduces fracture risk by increasing bone mass and improving bone microarchitecture. Teriparatide treatment reduces vertebral and non-vertebral fracture risk markedly in women and men with idiopathic osteoporosis, or with glucocorticoid-induced osteoporosis. Teriparatide should thus be considered as first line treatment for postmenopausal women and for men with severe osteoporosis

A single high dose of oral vitamin D3 is insufficient to correct a deficiency in a rheumatologic population

Introduction Vitamin D plays a major role in bone metabolismand neuromuscular function. Supplementation with vitamin D iseffective to reduce the risk of fall and of fracture. However adherenceto oral daily vitamin D is low. Screening and correcting vitamin Dinsufficiency in a rheumatologic population could improve bothmorbidity and quality of life. After determining the prevalence ofvitamin D deficiency in this population, we evaluated if supplementationwith a single high dose of oral 25-OH vitamin D3 wassufficient to correct this abnormality.Methods During one month (November 2009), levels of 25-OHvitamin D were systematically determined in our rheumatology outpatientclinic and classified in: vitamin D deficiency (< 10 μg/l),vitamin D insufficiency (10 to 30 μg/l) or normal vitamin D (> 30 μg/l).Patients with insufficiency or deficiency received respectively a singlehigh dose of 300'000 IU or 600'000 IU oral vitamin D3. In addition,all patients with osteoporosis were prescribed daily supplement ofcalcium (1 g) and vitamin D (800 IU). 25-OH vitamin D levels werereevaluated after 3 months.Results Vitamin D levels were initially determined in 292 patients(mean age 53, 211 women, 87 % Caucasian). 77 % had inflammatoryrheumatologic disease (IRD), 20 % osteoporosis (OP) and 12 %degenerative disease (DD). Vitamin D deficiency was present in 20(6.8 %), while 225 (77.1 %) had insufficiency. Of the 245 patientswith levels < 30μg/l, a new determination of vitamin D level wasavailable in 173 (71 %) at 3 months.Conclusion Vitamin D insufficiency is highly prevalent in ourrheumatologic population (84 %), and is not adequately correctedby a single high dose of oral vitamin D3 in > 50 % of the patientswith IRD and DD. In patients with OP, despite association of asingle high dose with daily oral vitamin D supplementation, 40 %of patients are still deficient when reevaluated at 3 months

High prevalence of hypovitaminosis D in a Swiss rheumatology outpatient population.

Vitamin D is important for bone metabolism and neuromuscular function. While a routine dosage is often proposed in osteoporotic patients, it is not so evident in rheumatology outpatients where it has been shown that the prevalence of hypovitaminosis D is high. The aim of the current study was to systematically evaluate the vitamin D status in our outpatient rheumatology population to define the severity of the problem according to rheumatologic diseases. During November 2009, all patients were offered a screening test for 25-OH vitamin D levels and categorised as deficient (<10 µg/l [ng/ml] [25 nmol/l]), insufficient (10 µg/l to 30 µg/l [25 to 75 nmol/l]) or normal (>30 µg/l [75 nmol/l]). A total of 272 patients were included. The mean 25-OH vitamin D level was 21 µg/l (range 1.5 to 45.9). A total of 20 patients had vitamin D deficiency, 215 patients had an insufficiency and 37 patients had normal results. In the group of patients with osteoporosis mean level of 25-OH vitamin D was 25 µg/l and 31% had normal results. In patients with inflammatory rheumatic diseases (N = 219), the mean level of 25-OH vitamin D was 20.5 µg/l, and only 12% had normal 25-OH vitamin D levels. In the small group of patients with degenerative disease (N = 33), the mean level of 25-OH vitamin D was 21.8 µg/l, and 21% had normal results. Insufficiency and deficiency were even seen in 38% of the patients who were taking supplements. These results confirm that hypovitaminosis D is highly prevalent in an outpatient population of rheumatology patients, affecting 86% of subjects. Despite oral supplementation (taken in 38% of our population), only a quarter of those on oral supplementation attained normal values of 25-OH vitamin D

What was your fracture risk evaluated by FRAX(®) the day before your osteoporotic fracture?

Osteoporotic fracture (OF) is one of the major causes of morbidity and mortality in industrialized countries. Switzerland is among the countries with the greatest risk. Our aim was (1) to calculate the FRAX(®) in a selected Swiss population the day before the occurrence of an OF and (2) to compare the results with the proposed Swiss FRAX(®) thresholds. The Swiss Association Against Osteoporosis proposed guidelines for the treatment of osteoporosis based on age-dependent thresholds. To identify a population at a very high risk of osteoporotic fracture, we included all consecutive patients in the active OF pathway cohort from the Lausanne University Hospital, Switzerland. FRAX(®) was calculated with the available data the day before the actual OF. People with a FRAX(®) body mass index (BMI) or a FRAX(®) (bone mineral density) BMD lower than the Swiss thresholds were not considered at high risk. Two-hundred thirty-seven patients were included with a mean age of 77.2 years, and 80 % were female. Major types of fracture included hip (58 %) and proximal humerus (25 %) fractures. Mean FRAX(®) BMI values were 28.0, 10.0, 13.0, 26.0, and 37.0 % for age groups 50-59, 60-69, 70-79, and 80-89 years old, respectively. Fifty percent of the population was not considered at high risk by the FRAX(®) BMI. FRAX(®) BMD was available for 95 patients, and 45 % had a T score < -2.5 standard deviation. Only 30 % of patients with a normal or osteopenic BMD were classified at high risk by FRAX(®) BMD. The current proposed Swiss thresholds were not able to classify at high risk in 50 to 70 % of the studied population the day before a major OF

Effects of anti-resorptive agents on trabecular bone score (TBS) in older women.

We evaluated the longitudinal effects of anti-resorptive agents (534 treated women vs. 1,150 untreated) on lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). TBS was responsive to treatment in women over age 50. The treatment-related increase in TBS was less than the increase in BMD, which is consistent with bone texture preservation. INTRODUCTION: In addition to inducing an increase in BMD, anti-resorptive agents also help to preserve bone architecture. TBS, a new gray-level texture measurement, correlates with 3D parameters of bone micro-architecture independent of BMD. Our objective was to evaluate the longitudinal effects of anti-resorptive agents on lumbar spine BMD and TBS. METHODS: Women (≥50 years), from the BMD program database for the province of Manitoba, Canada, who had not received any anti-resorptive drug prior to their initial dual X-ray absorptiometry (DXA) exam were divided into two groups: untreated, those without any anti-resorptive drug over the course of follow-up, and treated, those with a non-estrogen anti-resorptive drug (86 % bisphosphonates, 10 % raloxifene, and 4 % calcitonin). Lumbar spine TBS was calculated for each lumbar spine DXA examination. Changes in TBS and BMD between baseline and follow-up (mean follow-up 3.7 years), expressed in percentage per year, were compared between the two groups. RESULTS: A total of 1,150 untreated women and 534 treated women met the inclusion criteria. Only a weak correlation was seen between BMD and TBS in either group. Significant intergroup differences in BMD change and TBS change were observed over the course of follow-up (p < 0.001). Similar mean decreases in BMD and TBS (-0.36 %/year and -0.31 %/year, respectively) were seen for untreated subjects (both p < 0.001). Conversely, treated subjects exhibited a significant mean increase in BMD (+1.86 %/year, p < 0.002) and TBS (+0.20 %/year, p < 0.001). CONCLUSION: TBS is responsive to treatment with non-estrogen anti-resorptive drug therapy in women over age 50. The treatment-related increase in TBS is less than the increase in BMD, which is consistent with bone texture preservation

Can one or two high doses of oral vitamin D3 correct insufficiency in a non-supplemented rheumatologic population?

We evaluated the effectiveness of supplementation with high dose of oral vitamin D3 to correct vitamin D insufficiency. We have shown that one or two oral bolus of 300,000 IU of vitamin D3 can correct vitamin D insufficiency in 50% of patients and that the patients who benefited more from supplementation were those with the lowest baseline levels. INTRODUCTION: Adherence with daily oral supplements of vitamin D3 is suboptimal. We evaluated the effectiveness of a single high dose of oral vitamin D3 (300,000 IU) to correct vitamin D insufficiency in a rheumatologic population. METHODS: Over 1 month, 292 patients had levels of 25-OH vitamin D determined. Results were classified as: deficiency <10 ng/ml, insufficiency ≥10 to 30 ng/ml, and normal ≥30 ng/ml. We added a category using the IOM recommended cut-off of 20 ng/ml. Patients with deficient or normal levels were excluded, as well as patients already supplemented with vitamin D3. Selected patients (141) with vitamin D insufficiency (18.5 ng/ml (10.2-29.1) received a prescription for 300,000 IU of oral vitamin D3 and were asked to return after 3 (M3) and 6 months (M6). Patients still insufficient at M3 received a second prescription for 300,000 IU of oral vitamin D3. Relation between changes in 25-OH vitamin D between M3 and M0 and baseline values were assessed. RESULTS: Patients (124) had a blood test at M3. Two (2%) had deficiency (8.1 ng/ml (7.5-8.7)) and 50 (40%) normal results (36.7 ng/ml (30.5-5.5)). Seventy-two (58%) were insufficient (23.6 ng/ml (13.8-29.8)) and received a second prescription for 300,000 IU of oral vitamin D3. Of the 50/124 patients who had normal results at M3 and did not receive a second prescription, 36 (72%) had a test at M6. Seventeen (47%) had normal results (34.8 ng/ml (30.3-42.8)) and 19 (53%) were insufficient (25.6 ng/ml (15.2-29.9)). Of the 72/124 patients who receive a second prescription, 54 (75%) had a test at M6. Twenty-eight (52%) had insufficiency (23.2 ng/ml (12.8-28.7)) and 26 (48%) had normal results (33.8 ng/ml (30.0-43.7)). At M3, 84% patients achieved a 25-OH vitamin D level >20 ng/ml. The lowest the baseline value, the highest the change after 3 months (negative relation with a correlation coefficient r = -0.3, p = 0.0007). CONCLUSIONS: We have shown that one or two oral bolus of 300,000 IU of vitamin D3 can correct vitamin D insufficiency in 50% of patients

Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology

Quantitative ultrasound for the detection and management of osteoporosis.

Quantitative ultrasound (QUS) appears to be developing into an acceptable, low-cost and readily-accessible alternative to dual X-ray absorptiometry (DXA) measurements of bone mineral density (BMD) in the detection and management of osteoporosis. Perhaps the major difficulty with their widespread use is that many different QUS devices exist that differ substantially from each other, in terms of the parameters they measure and the strength of empirical evidence supporting their use. But another problem is that virtually no data exist outside of Caucasian or Asian populations. In general, heel QUS appears to be most tested and most effective. Some, but not all heel QUS devices are effective assessing fracture risk in some, but not all populations, the evidence being strongest for Caucasian females &gt; 55 years old, though some evidence exists for Asian females &gt; 55 and for Caucasian and Asian males &gt; 70. Certain devices may allow to estimate the likelihood of osteoporosis, but very limited evidence exists supporting QUS use during the initiation or monitoring of osteoporosis treatment. Likely, QUS is most effective when combined with an assessment of clinical risk factors (CRF); with DXA reserved for individuals who are not identified as either high or low risk using QUS and CRF. However, monitoring and maintenance of test and instrument accuracy, precision and reproducibility are essential if QUS devices are to be used in clinical practice; and further scientific research in non-Caucasian, non-Asian populations clearly is compulsory to validate this tool for more widespread use