[Show abstract][Hide abstract] ABSTRACT: Patients with a low bone mineral density have an increased risk of cardiovascular diseases (CVD) and venous thromboembolic events (VTE). The aim of our retrospective chart review was to investigate the prevalence of CVD, VTE, hypertension (HT), and diabetes mellitus type 2 (DM2) in patients with a recent clinical fracture visiting the Fracture Liaison Service (FLS). Out of 3057 patients aged 50-90 years, 1359 consecutive patients, who agreed and were able to visit the FLS for fracture risk evaluation, were included (71.7% women; mean age 65.2 yrs). Based on medical history, 29.9% had a history of CVD (13.7%), VTE (1.7%), HT (14.9%), and DM2 (7.1%) or a combination. Their prevalence increased with age (21% in patients aged 50-59 years to 48% in patients aged >80 years) and was higher in men than in women (36% versus 27%), but independent of bone mineral density and fracture type. Careful evaluation of medical history with respect to these risk factors should be performed in patients with a recent clinical fracture before starting treatment with medications that increase the risk of VTE or cardiovascular events, such as raloxifene, strontium ranelate, or NSAIDs.
BioMed Research International 08/2014; 2014:710945. DOI:10.1155/2014/710945 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Calcium and vitamin D play an essential role in bone metabolism but deficiency and/or inadequate intake are common.
To describe a practical approach based on the literature regarding clinically important aspects of calcium and vitamin D supplementation.
A systematic evaluation of relevant literature in Medline was conducted. We included physiological studies, publications on relevant guidelines, meta-analysis, randomized clinical trials, and cohort studies.
An adequate calcium intake and vitamin D supplementation is recommended in most guidelines xon fracture prevention. Daily supplementation with 800 IU is advocated in most guidelines, appears to be safe, and with this approach it is generally not necessary to determine vitamin D levels. There are no data on additional effects of loading doses of vitamin D on fracture or fall prevention. Calcium supplementation should be tailored to the patient’s need: usually 500 mg per day is required. The intestinal absorption of calcium citrate is approximately 24% better than that of calcium carbonate independent of intake with meals. Data on difference between calcium absorption with calcium carbonate compared to calcium citrate with simultaneous use of proton pump inhibitors are lacking. Concern has arisen about a possible link between calcium supplementation and an increased risk of myocardial infarction. Probably only well-designed prospective randomized controlled trials will be able to allow definite conclusions on this subject.
Daily supplementation with 800 IU vitamin D is a practical and safe strategy without the need for prior determination of vitamin D levels. Calcium supplementation should be tailored to the patient’s need based on total daily dietary calcium intake. In most patients 500 mg per day is required to achieve a total intake of 1,200 mg, or in some 1,000 mg per day. More calcium is absorbed from calcium citrate compared to calcium carbonate.
[Show abstract][Hide abstract] ABSTRACT: Type 2 diabetes mellitus has recently been linked to an increased fracture risk. Since bone mass seems to be normal to elevated in patient with type 2 diabetes, the increased fracture risk is thought to be due to both an increased falling frequency and decreased bone quality. The increased falling frequency is mainly a result of complications of the disease such as a retinopathy and polyneuropathy. Bone quality is affected through changes in bone shape, bone micro-architecture, and in material properties such as bone mineralization and the quality of collagen. Commonly used methods for predicting fracture risk such as dual energy X-ray absorptiometry and fracture risk assessment tools are helpful in patients with type 2 diabetes mellitus, but underestimate the absolute fracture risk for a given score. New imaging modalities such as high resolution peripheral quantitative computed tomography are promising for giving insight in the complex etiology underlying the fragility of the diabetic bone, as they can give more insight into the microarchitecture and geometry of the bone. We present an overview of the contributing mechanisms to the increased fracture risk and the usefulness of imaging modalities and risk assessment tools in predicting fracture risk in patients with type 2 diabetes.
[Show abstract][Hide abstract] ABSTRACT: Purpose of review:
The purpose of this review is to provide guidance to clinicians about which laboratory tests should be performed in patients with osteoporosis or with a recent fracture.
Newly diagnosed secondary osteoporosis and other metabolic bone diseases (SECOB) have been found in 5-48% of patients with osteoporosis. In patients with a recent fracture, new SECOB is found in 10-47% of patients with osteoporosis, and in 26-51% if all patients with a fracture regardless of bone mineral density (BMD) are screened. More than one SECOB can be found in the same patient, even when they have already known SECOB. In primary hyperparathyroidism, hyperthyroidism, hypercortisolism, and multiple myeloma, both SECOB and its treatment have an impact on BMD and fractures. For other SECOBs, no treatment is available, or there are no data about the effect of treatment of the SECOB on BMD and fractures.
We recommend performing the following tests in all patients with osteoporosis or a recent clinical fracture: calcium, phosphate, creatinine, albumin, erythrocyte sedimentation rate in all patients, 24 h urine calcium in men and serum testosterone in men less than 70 years. On indication, additional tests can be performed.
Current Opinion in Rheumatology 07/2014; 26(4):430-439. DOI:10.1097/BOR.0000000000000074 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recommendations for daily calcium intake from dairy products are variable and based on local consensus. To investigate whether patients with a recent fracture complied with these recommendations, we quantified the daily dairy calcium intake including milk, milk drinks, pudding, yoghurt, and cheese in a Dutch cohort of fracture patients and compared outcomes with recent data of a healthy U.S. cohort (80% Caucasians). An observational study analyzed dairy calcium intakes of 1526 female and 372 male Dutch fracture patients older than 50. On average, participants reported three dairy servings per day, independently of age, gender or population density. Median calcium intake from dairy was 790 mg/day in females and males. Based on dairy products alone, 11.3% of women and 14.2% of men complied with Dutch recommendations for calcium intake (adults ≤ 70 years: 1100 mg/day and >70 years: 1200 mg/day). After including 450 mg calcium from basic nutrition, compliance raised to 60.5% and 59.1%, respectively, compared to 53.2% in the U.S. cohort. Daily dairy calcium intake is not associated with femoral neck bone mineral density (BMD) T-scores or WHO Fracture Assessment Tool (FRAX) risk scores for major fracture or hip fracture. However, when sub analyzing the male cohort, these associations were weakly negative. The prevalence of maternal hip fracture was a factor for current fracture risks, both in women and men. While daily dairy calcium intake of Dutch fracture patients was well below the recommended dietary intake, it was comparable to intakes in a healthy U.S. cohort. This questions recommendations for adding more additional dairy products to preserve adult skeletal health, particularly when sufficient additional calcium is derived from adequate non-dairy nutrition.
[Show abstract][Hide abstract] ABSTRACT: A fracture liaison service model of care is widely recommended and applied, but data on its effectiveness are scarce. Therefore, the risk of subsequent nonvertebral fractures and mortality within two years after a nonvertebral fracture was analyzed in patients who presented to a hospital with a fracture liaison service and a hospital without a fracture liaison service.
In 2005 to 2006, all consecutive patients with an age of fifty years or older presenting with a nonvertebral fracture were included. In the group that presented to a hospital without a fracture liaison service (the no-FLS group), only standard fracture care procedures were followed to address proper fracture-healing. In the group that presented to a hospital with a fracture liaison service (the FLS group), dual x-ray absorptiometry scans and laboratory testing were performed, and if applicable, patients were treated according to the Dutch guideline for osteoporosis. The risk for subsequent nonvertebral fracture and mortality were analyzed using multivariable Cox regression models with adjustments for age, sex, and baseline fracture location.
In total, 1412 patients presented to the fracture liaison service (73.2% were women, and the mean age was 71.1 years), and 1910 underwent standard fracture care (69.8% were women, and the mean age was 69.5 years). After adjustment for age, sex, and baseline fracture location, patients who attended the fracture liaison service had a significantly lower mortality risk (hazard ratio: 0.65; 95% confidence interval [CI]: 0.53 to 0.79) over two years of follow-up. The subsequent nonvertebral fracture risk was also significantly lower in the patients in the FLS group, but this effect was time-dependent, with a hazard ratio of 0.84 (95% CI: 0.64 to 1.10) at twelve months and 0.44 (95% CI: 0.25 to 0.79) at twenty-four months.
Patients seen at the fracture liaison service had a significantly lower mortality and subsequently a lower risk of nonvertebral fracture than those not seen at the fracture liaison service, with a reduction of 35% and 56%, respectively, over two years of follow-up. A fracture liaison service appears to be a successful approach to reduce the number of subsequent fractures and premature mortality in this cohort of patients.
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
The Journal of Bone and Joint Surgery 02/2014; 96(4):e29. DOI:10.2106/JBJS.L.00223 · 5.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: The aim of this study was to review factors that influence serum 25(OH)D when giving vitamin D3 supplements.
Research methods and procedures: From a comprehensive search of all randomized controlled clinical trials (RCTs) with vitamin D3 supplementation available on PubMed up to November 2011, we selected 33 RCTs with 43 treatment arms that included at least 30 adult subjects. The achieved pooled mean difference (PMD) and 95% confidence intervals (CIs) were calculated using the random-effects models. Meta-regression and subgroup analyses was performed for pre-specified factors, including dose, duration, baseline serum 25(OH)D and age.
Results: With a mean baseline serum 25(OH)D of 50.4 nmol/L, PMD was 37.0 nmol/L (CI:33.0 to 41.0) with significant heterogeneity among studies. Dose (slope: 0.006, p<0.001), trial duration (slope: 0.21, p<0.001), baseline serum 25(OH)D (slope:-0.19, p<0.001) and age (slope: 0.42, p<0.001) independently influenced vitamin D response. Similar results were found in studies with a mean baseline serum 25(OH)D <50 nmol/L. In sub-group analyses the PMD was higher with doses of ≥800 IU/day (39.3 nmol/L) after 6-12 months (41.7 nmol/L),with baseline 25(OH)D below 50 nmol/L (39.6 nmol/L) and in elderly (40.5 nmol/L in subjects older than 80 years).
Conclusion: This meta regression indicates that a higher increase in serum levels of 25(OH)D in adults is found with a dose of ≥800 IU/day, after at least 6-12 months, and even when baseline 25(OH)D is low and in the oldest elderly.
[Show abstract][Hide abstract] ABSTRACT: There are two commonly used fracture risk prediction tools FRAX(®) and Garvan Fracture Risk Calculator (GARVAN-FRC). The objective of this study was to investigate the utility of these tools in daily practice.
A prospective population-based 5-year follow-up study was conducted in ten general practice centres in the Netherlands. For the analyses, the FRAX(®) and GARVAN-FRC 10-year absolute risks (FRAX(®) does not have 5-year risk prediction) for all fractures were used.
Among 506 postmenopausal women aged ≥60 years (mean age: 67.8±5.8 years), 48 (9.5%) sustained a fracture during follow-up. Both tools, using BMD values, distinguish between women who did and did not fracture (10.2% vs. 6.8%, respectively for FRAX(®) and 32.4% vs. 39.1%, respectively for GARVAN-FRC, p<0.0001) at group level. However, only 8.9% of those who sustained a fracture had an estimated fracture risk ≥20% using FRAX(®) compared with 53.3% using GARVAN-FRC. Although both underestimated the observed fracture risk, the GARVAN-FRC performed significantly better for women who sustained a fracture (higher sensitivity) and FRAX(®) for women who did not sustain a fracture (higher specificity). Similar results were obtained using age related cut off points.
The discriminant value of both models is at least as good as models used in other medical conditions; hence they can be used to communicate the fracture risk to patients. However, given differences in the estimated risks between FRAX(®) and GARVAN-FRC, the significance of the absolute risk must be related to country-specific recommended intervention thresholds to inform the patient.
[Show abstract][Hide abstract] ABSTRACT: An increasing number of generic alendronate formulations have become available. Although expected to have the same tolerability and efficacy, head-to head comparison of generic and brand alendronate was never performed. Therefore, we compared the tolerability and efficacy of generic and brand alendronate.
In a randomized double-blinded single centre cross-over study in 37 postmenopausal women (mean age 65.4±6.4 years) with osteoporosis were treated with generic and branded alendronate during 24 (2x12) weeks. Tolerance was evaluated by the Gastro intestinal Symptom Rating Scale (GSRS) and self-reported side effects. Efficacy was assessed by serum bone turnover markers, carboxy terminal telopeptide (CTX) and procollagen type I N-terminal propeptide (PINP). No wash out period was allowed (ethical reasons). Because of possible carry over effect only data of the first 12 weeks were analyzed using linear mixed models.
There were no significant differences in overall tolerance (GSRS) between treatment groups. However, for subscale abdominal pain, patients using generic had a significantly higher mean GSRS score at week 4 (estimated mean difference (B): 0.40; 95%CI: 0.05 to 0.74, p = 0.024). The level of bone turnover markers significantly decreased over 12 weeks of follow-up for generic and branded alendronate (p < 0.001). Mean level of CTX was significantly lower with branded at week 4 (B: 121.3; 95%CI: 52.0 to 190.5), but not at week 12 (B: 53.6; 95%CI:-3.7 to 110.9). No significant differences were found for PINP at week 4 or 12.
Bone turnover markers were significantly reduced with branded and generic alendronate. With branded, CTX was significantly lower at 4 weeks. Generic caused significantly higher abdominal pain scores in the first 4 weeks of treatment. Therefore, generic alendronate may not have the same tolerability and efficacy as branded alendronate in the first weeks after starting treatment in patients with a recent fracture.
Dutch Trial Register NTR number 1867 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1867.
PLoS ONE 10/2013; 8(10):e78153. DOI:10.1371/journal.pone.0078153 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 49-year-old woman was examined for osteoporosis and metabolic bone disease after a low-trauma wrist fracture. Laboratory and additional radiological investigations revealed parathyroid hormone (PTH)-mediated hypercalcaemia caused by a parathyroid adenoma. A second patient, a 65-year-old woman with a history of abdominal complaints and tetany, appeared to have hypocalcaemia. Severe vitamin D deficiency and secondary hyperparathyroidism were detected and the patient was finally diagnosed with coeliac disease. Based on these case studies, we highlight the calcium homeostasis and the role of laboratory evaluation of serum calcium, inorganic phosphate, intact PTH, 25-OH vitamin D, magnesium and 24-hour urinary calcium excretion in the diagnostic work-up for hypocalcaemia and hypercalcaemia.
Nederlands tijdschrift voor geneeskunde 01/2012; 156(6):A3919.
[Show abstract][Hide abstract] ABSTRACT: Falls are one of the main causes of fractures in elderly people and after a recent fracture, the risk of another fall is increased, resulting in subsequent fracture. Therefore, risk factors for future falls should be determined. We prospectively investigated the relationship between depression and the incidence of falls in post-menopausal women after a low-energy fracture.
At baseline, 181 women aged 60 years and older who presented with a recent low-energy fracture were evaluated at the fracture and osteoporosis outpatient clinics of two hospitals. As well as clinical evaluation and bone mineral density tests, the presence of depression (measured using the Edinburgh Depression Scale, EDS, depression cut-off > 11) and risk factors for falling were assessed. During two years of follow-up, the incidence of falls was registered annually by means of detailed questionnaires and interviews.
Seventy-nine (44%) of the women sustained at least one fall during follow-up. Of these, 28% (n = 22) suffered from depression at baseline compared to 10% (n = 10) of the 102 women who did not sustain a fall during follow-up (Χ(2) = 8.76, df = 1, p = .003). Multiple logistic regression showed that the presence of depression and co-morbidity at baseline were independently related to falls (OR = 4.13, 95% CI = 1.58-10.80; OR = 2.25, 95% CI = 1.11-4.56, respectively) during follow-up.
The presence of depression in women aged 60 years and older with recent low-energy fractures is an important risk factor for future falls. We propose that clinicians treating patients with recent low-energy fractures should anticipate not only on skeletal-related risk factors for fractures, but also on fall-related risk factors including depression.
[Show abstract][Hide abstract] ABSTRACT: The identification of vertebral fractures (VFs) is important for decisions on fracture prevention. Vertebral fracture assessment (VFA) was shown to be a patient-friendly and valid method for detecting undiagnosed VFs in (Dutch) women. However, this has only been investigated in women seeking care at secondary or tertiary institutions.
To investigate the prevalence of previously undiagnosed VFs in women in Dutch primary care using VFA.
A total of 566 Dutch women aged 50 years and older (mean age, 69 years; SD=8.4) with clinical risk factors (CRFs) for fractures volunteered for dual-energy X-ray absorptiometry (DXA) measurement and VFA. VFs were defined semi-quantitatively using Genant's method.
One CRF was present in each of 130 women, 274 had two, and 162 women had more than two CRFs. In 120 (21%) of the women, previously unknown osteoporosis (T-score ≤ -2.5SD) was diagnosed, and in 174 (31%), a previously undiagnosed moderate or severe VF was found. No osteoporosis was found in 130 (75%) of the women with a VF. Based on the outcome of DXA, 21% of the women were eligible for treatment, while the combination of DXA and VFA resulted in a total of 250 (44%) women requiring treatment.
The percentage of previously unknown VFs diagnosed by VFA in women aged 50 years and older with one or more CRFs for fractures in primary care is high. When only using BMD measurements, only half the women eligible for treatment would actually receive this. We recommend performing VFA in all women aged 50 years and older who are referred for DXA based on Dutch case finding criteria.
[Show abstract][Hide abstract] ABSTRACT: We discussed whether we are able to select a subgroup of patients with osteopenia having a high fracture risk, in which anti-osteoporotic drug treatment can be advocated. We concluded that in individuals in whom, based on clinical risk factors, a dual-energy x-ray absorptiometry (DXA) was performed in which osteopenia was diagnosed, anti-osteoporotic treatment should be prescribed in those patients with prevalent vertebral fractures, and in patients chronically using glucocorticoids, in a dosage of 7.5 mg per day or more. Although recent developments with regard to high-resolution imaging techniques (eg, peripheral quantitative computed tomography) seem to be promising, until now they do not provide substantial more reliable information than DXA in the prediction of fractures. We think that more data are urgently needed, since safe and effective drugs are available, but there is uncertainty to which patients with osteopenia these drugs should be prescribed.
Current Osteoporosis Reports 06/2011; 9(3):167-72. DOI:10.1007/s11914-011-0062-3
[Show abstract][Hide abstract] ABSTRACT: Previously undetected contributors to secondary osteoporosis and metabolic bone diseases (SECOB) are frequently found in patients with osteoporosis, but the prevalence in patients at the time they present with a clinical fracture is unknown.
All consecutive patients with a recent clinical vertebral or nonvertebral fracture, who were able and willing to be investigated (n = 626: 482 women, 144 men, age range 50-97 yr) had bone mineral density and laboratory investigations (serum calcium, inorganic phosphate, 25-hydroxyvitamin D, creatinine, intact PTH, TSH, free T(4), serum and urine protein electrophoresis, and in men also serum testosterone).
Known SECOB contributors were present in 23.0% of patients and newly diagnosed SECOB contributors in 26.5%: monoclonal proteinemia (14 of 626), renal insufficiency grade III or greater (54 of 626), primary (17 of 626) and secondary (64 of 626) hyperparathyroidism, hyperthyroidism (39 of 626), and hypogonadism in men (12 of 144). Newly diagnosed SECOBs, serum 25-hydroxyvitamin D less than 50 nmol/liter (in 63.9%), and dietary calcium intake less than 1200 mg/d (in 90.6%) were found at any age, in both sexes, after any fracture (except SECOB in men with finger and toe fractures) and at any level of bone mineral density.
At presentation with a fracture, 26.5% of patients have previously unknown contributors to SECOB, which are treatable or need follow-up, and more than 90% of patients have an inadequate vitamin D status and/or calcium intake. Systematic screening of patients with a recent fracture identifies those in whom potentially reversible contributors to SECOB and calcium and vitamin D deficiency are present.
The Journal of Clinical Endocrinology and Metabolism 03/2011; 96(5):1360-7. DOI:10.1210/jc.2010-2135 · 6.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inadequate serum 25-hydroxyvitamin D (25[OH]D) concentrations are associated with muscle weakness, decreased physical performance, and increased propensity in falls and fractures. This paper discusses several aspects with regard to vitamin D status and supplementation when treating patients with osteoporosis in relation to risks and prevention of falls and fractures. Based on evidence from literature, adequate supplementation with at least 700 IU of vitamin D, preferably cholecalciferol, is required for improving physical function and prevention of falls and fractures. Additional calcium supplementation may be considered when dietary calcium intake is below 700 mg/day. For optimal bone mineral density response in patients treated with antiresorptive or anabolic therapy, adequate vitamin D and calcium supplementation is also necessary. Monitoring of 25(OH)D levels during follow-up and adjustment of vitamin D supplementation should be considered to reach and maintain adequate serum 25(OH)D levels of at least 50 nmol/L, preferably greater than 75 nmol/L in all patients.
Current Osteoporosis Reports 03/2011; 9(1):36-42. DOI:10.1007/s11914-010-0041-0
[Show abstract][Hide abstract] ABSTRACT: The Precision(®) (Abbott Diabetes Care) point-of-care biosensor test strips are widely used by patients with diabetes and clinical laboratories for measurement of plasma β-hydroxybutyrate (β-HB) concentrations in capillary blood samples obtained by fingerstick. In the literature, this procedure has been validated only against the enzymatic determination of β-HB in venous plasma, i.e., the method to which the Precision(®) has been calibrated.
In this study, the Precision(®) Xceed was compared to a methodologically different and superior procedure: determination of β-HB by liquid chromatography tandem-mass spectrometry (LC-MS/MS) in capillary blood spots. Blood spots were obtained from the same fingerstick sample from out of which Precision(®) measurements were performed. Linearity was tested by adding varying amounts of standard to an EDTA venous whole blood matrix.
The Precision(®) was in good agreement with LC-MS/MS within the measuring range of 0.0-6.0 mmol/L (Passing and Bablok regression: slope=1.20 and no significant intercept, R=0.97, n=59). Surprisingly, the Precision(®) showed non-linearity and full saturation at concentrations above 6.0 mmol/L, which were confirmed by a standard addition experiment. Results obtained at the saturation level varied between 3.0 and 6.5 mmol/L.
The Precision(®) β-HB test strips demonstrate good comparison with LC-MS/MS. Inter-individual variation around the saturation level, however, is large. Therefore, we advise reporting readings above 3.0 as >3.0 mmol/L. The test is valid for use in the clinically relevant range of 0.0-3.0 mmol/L.
Clinical Chemistry and Laboratory Medicine 12/2010; 48(12):1781-4. DOI:10.1515/CCLM.2010.351 · 2.71 Impact Factor