Showing papers in "Osteoporosis International in 2005"

Estimates of optimal vitamin D status

Abstract: Vitamin D has captured attention as an important determinant of bone health, but there is no common definition of optimal vitamin D status. Herein, we address the question: What is the optimal circulating level of 25-hydroxyvitamin D [25(OH)D] for the skeleton? The opinions of the authors on the minimum level of serum 25(OH)D that is optimal for fracture prevention varied between 50 and 80 nmol/l. However, for five of the six authors, the minimum desirable 25(OH)D concentration clusters between 70 and 80 nmol/l. The authors recognize that the average older man and woman will need intakes of at least 20 to 25 mcg (800 to 1,000 IU) per day of vitamin D3 to reach a serum 25(OH)D level of 75 nmol/l. Based on the available evidence, we believe that if older men and women maintain serum levels of 25(OH)D that are higher than the consensus median threshold of 75 nmol/l, they will be at lower risk of fracture.

Body mass index as a predictor of fracture risk: A meta-analysis

Abstract: Low body mass index (BMI) is a well-documented risk factor for future fracture. The aim of this study was to quantify this effect and to explore the association of BMI with fracture risk in relation to age, gender and bone mineral density (BMD) from an international perspective using worldwide data. We studied individual participant data from almost 60,000 men and women from 12 prospective population-based cohorts comprising Rotterdam, EVOS/EPOS, CaMos, Rochester, Sheffield, Dubbo, EPIDOS, OFELY, Kuopio, Hiroshima, and two cohorts from Gothenburg, with a total follow-up of over 250,000 person years. The effects of BMI, BMD, age and gender on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson regression model in each cohort separately. The results of the different studies were then merged. Without information on BMD, the age-adjusted risk for any type of fracture increased significantly with lower BMI. Overall, the risk ratio (RR) per unit higher BMI was 0.98 (95% confidence interval [CI], 0.97–0.99) for any fracture, 0.97 (95% CI, 0.96–0.98) for osteoporotic fracture and 0.93 (95% CI, 0.91–0.94) for hip fracture (all p 0.30). After adjusting for BMD, these RR became 1 for any fracture or osteoporotic fracture and 0.98 for hip fracture (significant in women). The gradient of fracture risk without adjustment for BMD was not linearly distributed across values for BMI. Instead, the contribution to fracture risk was much more marked at low values of BMI than at values above the median. This nonlinear relation of risk with BMI was most evident for hip fracture risk. When compared with a BMI of 25 kg/m2, a BMI of 20 kg/m2 was associated with a nearly twofold increase in risk ratio (RR=1.95; 95% CI, 1.71–2.22) for hip fracture. In contrast, a BMI of 30 kg/m2, when compared with a BMI of 25 kg/m2, was associated with only a 17% reduction in hip fracture risk (RR=0.83; 95% CI, 0.69–0.99). We conclude that low BMI confers a risk of substantial importance for all fractures that is largely independent of age and sex, but dependent on BMD. The significance of BMI as a risk factor varies according to the level of BMI. Its validation on an international basis permits the use of this risk factor in case-finding strategies.

Assessment of fracture risk.

Abstract: The diagnosis of osteoporosis is based on the measurement of bone mineral density (BMD). There are a number of clinical risk factors that provide information on fracture risk over and above that given by BMD. The assessment of fracture risk thus needs to be distinguished from diagnosis to take account of the independent value of the clinical risk factors. These include age, a prior fragility fracture, a parental history of hip fracture, smoking, use of systemic corticosteroids, excess alcohol intake and rheumatoid arthritis. The independent contribution of these risk factors can be integrated by the calculation of fracture probability with or without the use of BMD. Treatment can then be offered to those identified to have a fracture probability greater than an intervention threshold.

Epidemiology of osteoporotic fractures

Abstract: Several osteoporotic fractures such as hip fractures have a very high morbidity and mortality, and there are similar new findings for vertebral fractures. There have been several definitions of an osteoporotic fracture, and recently updated definitions have specified fractures occurring at a site associated with low BMD and which increase in incidence after the age of 50 years. Other definitions are based on clinical diagnosis. Lifetime risk of any osteoporotic fracture is very high and lies within the range of 40-50% in women and 13-22% for men. Measuring the true burden of osteoporotic fractures involves multiplying the morbidity of hip fractures according to age group: for women aged 50-54 years, the disability caused by osteoporotic fractures is 6.07 times that accounted for by hip fracture alone, and for women aged 80-84 years, the incidence of hip fractures should be multiplied by 1.55; for men aged 50-54 years, the incidence of hip fractures should be multiplied by 4.48, and for those aged 80-84 years by 1.50.

Smoking and fracture risk: a meta-analysis

Abstract: Smoking is widely considered a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex and bone mineral density (BMD). We studied 59,232 men and women (74% female) from ten prospective cohorts comprising EVOS/EPOS, DOES, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, Hiroshima and two cohorts from Gothenburg. Cohorts were followed for a total of 250,000 person-years. The effect of current or past smoking, on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex and BMD. The results of the different studies were merged using the weighted beta-coefficients. Current smoking was associated with a significantly increased risk of any fracture compared to non-smokers (RR=1.25; 95% Confidence Interval (CI)=1.15-1.36). Risk ratio (RR) was adjusted marginally downward when account was taken of BMD, but it remained significantly increased (RR=1.13). For an osteoporotic fracture, the risk was marginally higher (RR=1.29; 95% CI=1.13-1.28). The highest risk was observed for hip fracture (RR=1.84; 95% CI=1.52-2.22), but this was also somewhat lower after adjustment for BMD (RR=1.60; 95% CI=1.27-2.02). Risk ratios were significantly higher in men than in women for all fractures and for osteoporotic fractures, but not for hip fracture. Low BMD accounted for only 23% of the smoking-related risk of hip fracture. Adjustment for body mass index had a small downward effect on risk for all fracture outcomes. For osteoporotic fracture, the risk ratio increased with age, but decreased with age for hip fracture. A smoking history was associated with a significantly increased risk of fracture compared with individuals with no smoking history, but the risk ratios were lower than for current smoking. We conclude that a history of smoking results in fracture risk that is substantially greater than that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.

Alcohol intake as a risk factor for fracture.

Abstract: High intakes of alcohol have adverse effects on skeletal health, but evidence for the effects of moderate consumption are less secure. The aim of this study was to quantify this risk on an international basis and explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 5,939 men and 11,032 women from three prospectively studied cohorts comprising CaMos, DOES, and the Rotterdam Study. Cohorts were followed for a total of 75,433 person-years. The effect of reported alcohol intake on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined included age and BMD. The results of the different studies were merged using weighted beta-coefficients. Alcohol intake was associated with a significant increase in osteoporotic and hip fracture risk, but the effect was nonlinear. No significant increase in risk was observed at intakes of 2 units or less daily. Above this threshold, alcohol intake was associated with an increased risk of any fracture (risk ratio [RR] = 1.23; 95% CI, 1.06-1.43), any osteoporotic fracture (RR = 1.38; 95% CI, 1.16-1.65), or hip fracture (RR = 1.68; 95% CI, 1.19-2.36). There was no significant interaction with age, BMD, or time since baseline assessment. Risk ratios were moderately but not significantly higher in men than in women, and there was no evidence for a different threshold for effect by gender. We conclude that reported intake of alcohol confers a risk of some importance beyond that explained by BMD. The validation of this risk factor on an international basis permits its use in case-finding strategies.

Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam Study.

Abstract: The aim of this study was to determine the association between type-2 diabetes mellitus (DM), BMD and fractures in 6,655 men and women aged 55 years and over from the Rotterdam Study. We compared subjects with type-2 DM to subjects without DM. Additionally, subset analyses were performed, dividing subjects on the basis of the glucose tolerance test into already treated DM, newly diagnosed DM, impaired glucose tolerance (IGT) and normal glucose tolerance (NGT, reference). Femoral neck and lumbar spine BMD were measured using DEXA. Nonvertebral fracture ascertainment was performed using an automated record system involving GPs and local hospitals. Although subjects with DM had higher BMD, they had an increased nonvertebral fracture risk: hazard ratio (HR) 1.33 (1.00-1.77). In subset analysis, the increased fracture risk appeared restricted to treated DM subjects only: HR 1.69 (1.16-2.46). Subjects with IGT had a higher BMD, but contrary to treated DM, they had a lower fracture risk: HR 0.80 (0.63-1.00). In conclusion, subjects with type-2 DM and IGT both have a higher BMD. Whereas, subjects with IGT have a decreased fracture risk, subjects with DM (primarily those with already established and treated DM) had an increased fracture risk, probably due to long-term complications associated with DM.

Requirements for DXA for the management of osteoporosis in Europe

Abstract: The availability of dual energy X-ray absorptiometry (DXA) varies markedly in different countries. There is, however, little information to indicate the optimal requirements for this technology. The principal aim of this study was to estimate the requirements for DXA in Europe for the assessment and treatment of osteoporosis. Three assessment scenarios were chosen. The first envisaged screening of all women with DXA at the age of 65 years. A second scenario comprised a screening programme based on the identification of clinical risk factors with the selective addition of BMD tests in those close to an intervention threshold. The third scenario envisaged a case finding strategy where women aged 65 years were identified on the basis of risk factors and referred for DXA. Requirements for women aged more than 65 years were amortised over a 10-year period. A secondary aim was to estimate the number and cost of osteoporotic fractures in Europe. The requirements for DXA in assessment ranged from 4.21 to 11.21 units/million of the population. The most efficient assessment scenario was the use of clinical risk factors with the selective use of BMD. With this scenario, an additional 6.39 units/million would be required to monitor treatment giving a total requirement of 10.6 units/million. In 2000, the number of osteoporotic fractures was estimated at 3.79 million, of which 0.89 million were hip fractures (179,000 hip fractures in men and 711,000 in women). The total direct costs were estimated at 31.7 billion Euros (21.165 billion UK pounds), which were expected to increase to 76.7 billion Euros (51.1 billion UK pounds) in 2050 based on the expected changes in the demography of Europe.

Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women.

Abstract: Vitamin D supplements have been used to prevent fractures. The effect may be mediated through increased bone mass, but also through reduced falling propensity. The aim of this study was to evaluate the association between 25-hydroxy vitamin D levels (25OHD), fall-associated variables (including tests of functional performance), and fracture in ambulatory women. At baseline 25OHD was measured in 986 women. Fall-associated variables were investigated at baseline. Fractures were recorded during a 3-year follow-up. Four percent of the women had 25OHD levels below 20 ng/ml (50 nmol/l), and 26% had 25OHD levels below 30 ng/ml (75 nmol/l). 25OHD correlated with gait speed ( r =0.17, P <0.001), the Romberg balance test ( r =0.14, P <0.001), self-estimated activity level ( r =0.15, P <0.001), and thigh muscle strength ( r =0.08, P =0.02). During the 3-year follow-up, 119 out of the 986 women sustained at least one fracture. The Cox proportional hazard ratio (HR) (95% confidence interval) for sustaining a fracture during the follow-up was 2.04 (1.04–4.04) for the group of women with 25OHD below 20 ng/ml, in which 9 out of 43 women sustained a fracture. Thirty-two of the 256 women with 25OHD levels below 30 ng/ml sustained a fracture during the follow-up, with a non-significant HR of 1.07 (1.07–1.61). This cohort of elderly, ambulatory women had a high mean 25OHD. A low 25OHD was associated with inferior physical activity level, gait speed and balance. A 25OHD level below 30 ng/ml was not associated with an increased risk of fractures in this study. However, a subgroup of women with 25OHD levels below 20 ng/ml had a tendency to an increased risk of fractures, which may be associated with an inferior physical activity and postural stability.

Quality of life in patients with osteoporosis

Abstract: Complaints regarding, and morbidity of, osteoporosis are caused by fractures which are associated with pain and decrease of physical function, social function, and well-being. These are aspects of quality of life. Health-related quality of life covers physical, mental, and social well-being. Quality of life may be measured for evaluation of treatment effects in clinical trials, for the assessment of the burden of the disease of osteoporosis, and for estimates of the cost-effectiveness of different treatment scenarios in health care policy. Quality of life has been measured in patients with osteoporosis with generic questionnaires such as SF-36 and EQ-5D, which can be used in many diseases, or with one of the six available osteoporotic-specific questionnaires, e.g., Qualeffo-41 or OPAQ. Every questionnaire has to be validated to assess psychometric properties and discrimination power between patients with osteoporosis and control subjects. The value attached to specific health states (utility) can be assessed with some generic instruments or by systematic questioning of the patient, e.g., the time-trade-off method. This results in one value for health status ranging from 0 (death) to 1 (perfect health). Utility values can be used to calculate loss of quality-adjusted life years (QALY). Most data have been obtained in patients with prevalent vertebral fractures. Scores of specific and generic questionnaires showed significant loss of quality of life with prevalent vertebral fractures. In addition, studies with Qualeffo-41 and OPAQ showed a deteriorating quality of life with increasing number of vertebral fractures. Lumbar fractures had more impact on quality of life than thoracic fractures. Incident vertebral fractures were also associated with a decrease of quality of life especially in the physical function domain. This applied to clinical incident vertebral fractures as well as to subclinical fractures to a lesser degree. Loss of quality of life following hip fracture has been documented with generic and osteoporosis-specific questionnaires. A considerable loss was observed in the 1st year with some improvement in the 2nd year, but not to baseline values. Quality of life depended on comorbidity, mobility, activities of daily life (ADL)-independence, and fracture complaints. Utility loss has been observed following hip fracture, especially disabling hip fracture, hip and vertebral fracture combined, or multiple vertebral fractures. Utility following osteoporotic fractures has been valued by patients, the healthy elderly, and panels of experts. The healthy elderly gave the worse quality-of-life scores (lower utility) to various hip fractures than patients with hip fractures themselves. In conclusion, suitable instruments exist for measuring quality of life in patients with osteoporotic fractures. These instruments are useful for clinical trials and for assessment of the burden of disease.

Balance disorder and increased risk of falls in osteoporosis and kyphosis: significance of kyphotic posture and muscle strength

Abstract: This controlled trial was designed to investigate the influence of osteoporosis-related kyphosis (O-K) on falls. Twelve community-dwelling women with O-K (Cobb angle, 50–65° measured from spine radiographs) and 13 healthy women serving as controls were enrolled. Mean age of the O-K group was 76 years (±5.1), height 158 cm (±5), and weight 61 kg (±7.9), and mean age of the control group was 71 years (±4.6), height 161 cm (±3.8), and weight 66 kg (±11.7). Quantitative isometric strength data were collected. Gait was monitored during unobstructed level walking and during stepping over an obstacle of four different heights randomly assigned (2.5%, 5%, 10%, and 15% of the subject’s height). Balance was objectively assessed with computerized dynamic posturography consisting of the sensory organization test. Back extensor strength, grip strength, and all lower extremity muscle groups were significantly weaker in the O-K group than the control group ( P <0.05), except right ankle plantar flexors ( P =0.09). There was a significant difference in the anteroposterior and mediolateral displacements and velocities. The O-K subjects had less anteroposterior displacement, greater mediolateral displacement, reduced anteroposterior velocity, and increased mediolateral velocity compared with controls for all conditions of unobstructed and obstructed level walking. Obstacle height had a significant effect on all center-of-mass variables. The O-K subjects had significantly greater balance abnormalities on computerized dynamic posturography than the control group ( P =0.002). Data show that thoracic hyperkyphosis on a background of reduced muscle strength plays an important role in increasing body sway, gait unsteadiness, and risk of falls in osteoporosis.

Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy.

Abstract: Teriparatide (rhPTH[1-34]), a bone-forming agent for the treatment of osteoporosis, increases bone mineral density in men and women, and reduces the risk of fractures in women with osteoporosis. However, fracture efficacy has not yet been confirmed in men. Further, there is limited information on the effect of withdrawal of teriparatide. The purpose of this manuscript is to report on bone mineral density and vertebral fracture incidence during a 42-month observation period, from the baseline of the previously reported treatment study in men [1] through 30 months of posttreatment follow-up. Three hundred fifty-five men who were treated with once-daily self-injections of either placebo or 20 or 40 µg of teriparatide participated in the follow-up study. Bone mineral density gradually decreased following discontinuation of teriparatide therapy. However, the lumbar spine and total hip values remained significantly higher than baseline after 30 months of follow-up (p≤0.001). Antiresorptive treatment prevented the decline and tended to further increase bone mineral density. Lateral thoracic lumbar radiographs obtained at baseline and 18 months after discontinuation of teriparatide were available for 279 men. Of these men, 11.7% assigned to placebo, 5.4% treated with teriparatide 20 µg, and 6.0% treated with teriparatide 40 µg had an incident vertebral fracture. In the combined teriparatide treated groups vs placebo, the risk of vertebral fracture was reduced 51% (nonsignificant, p=0.07). The incidence of moderate or severe fractures was significantly reduced by 83% (p=0.01). In conclusion, men who received teriparatide and who may have received follow-up antiresorptive therapy had a decreased risk of moderate and severe vertebral fractures.

Mechanics and mechano-biology of fracture healing in normal and osteoporotic bone

Abstract: Fracture repair, which aims at regaining the functional competence of a bone, is a complex and multifactorial process. For the success of fracture repair biology and mechanics are of immense importance. The biological and mechanical environments must be compatible with the processes of cell and tissue proliferation and differentiation. The biological environment is characterized by the vascular supply and by many biochemical components, the biochemical milieu. A good vascular supply is a prerequisite for the initiation of the fracture repair process. The biochemical milieu involves complex interactions among local and systemic regulatory factors such as growth factors or cytokines. The mechanical environment is determined by the local stress and strain within the fracture. However, the local stress and strain is not accessible, and the mechanical environment, therefore, is described by global mechanical factors, e.g., gap size or interfragmentary movement. The relationship between local stress and strain and the global mechanical factors can be obtained by numerical models (Finite Element Model). Moreover, there is considerable interaction between biological factors and mechanical factors, creating a biomechanical environment for the fracture healing process. The biomechanical environment is characterized by osteoblasts and osteocytes that sense the mechanical signal and express biological markers, which effect the repair process. This review will focus on the effects of biomechanical factors on fracture repair as well as the effects of age and osteoporosis.

Factors associated with the lumbar spine and proximal femur bone mineral density in older men

Abstract: Bone mass is a major determinant of fracture, but there have been few comprehensive studies of the correlates of bone mineral density (BMD) in older men. The objective of the current cross-sectional analysis was to determine the factors associated with BMD of the lumbar spine and proximal femur in a large population-based sample of older men enrolled in The Osteoporotic Fractures in Men Study, "Mr.OS." We enrolled 5,995 men 65 years of age or older, 89% Caucasian, in Mr.OS at six US clinical centers. Demographic, medical and family history and lifestyle information was obtained by interview and physical function and anthropometric data by examination. Spine and hip BMD was measured using dual-energy X-ray absorptimetry. The multivariable linear regression models predicted 19 and 10% of the overall variance in BMD of the femoral neck and spine, respectively. African-American men had 6 to 11% higher BMD than Caucasian men independent of multiple factors. Hip BMD declined with advancing age, while spine BMD increased. Body weight (per 10 kg) and self report of diabetes were each associated with 2 to 4% higher BMD, while history of a non-trauma fracture and current use of selective serotonin reuptake inhibitors, but not other antidepressants, were associated with at least 4% lower BMD. Both maternal and paternal histories of fracture were associated with 1.4-1.7% lower BMD. Osteoarthritis, physical activity, grip strength, alcohol intake, and dietary calcium were positively related to BMD, while a history of chronic lung disease, prostate cancer, and kidney stones was associated with lower BMD. Smoking, caffeine intake, and thiazide diuretics were not related to BMD in older men. A number of lifestyle and behavioral characteristics and medical conditions were associated with BMD in older men. Identification of these correlates could improve methods to identify men at risk for fracture and improve our understanding of fracture etiology.

Animal models for fracture treatment in osteoporosis.

Abstract: Demographic changes in the age structure of occidental populations are giving rise to osteoporosis and associated fractures, which are becoming a major public health burden. Various animal models have been established and used to investigate the pathogenesis of osteoporosis and to facilitate the preclinical testing of new treatment options such as antiresorptive drugs. Although osteoporosis can be induced in animals, spontaneous fractures without adequate trauma were only found in nonhuman primates. An animal model designed to investigate new ways to treat fractures of osteoporotic bone has to fulfill requirements that are very different from those of pharmacological testing. The aspects of major interest in orthopedic applications are bone fragility, efficacy of implant fixation and bone healing. Existing animal models for osteoporosis were critically reviewed focusing on these aspects. The advantages and disadvantages of the models with regard to their application in the testing of new fracture-fixation devices or biological approaches to stimulate bone healing are discussed. Ovariectomy alone does not cause the bone loss seen in osteoporotic human patients. New models to simulate fracture of osteoporotic bone need to be explored and used to address the specific aims of an experiment.

Fractures of the proximal humerus in osteoporotic bone

Abstract: The purpose of this article was to review critically the current treatment options for fractures of the proximal humerus in patients with severe osteoporosis. The main difficulties lie in correctly diagnosing the fracture and hence selecting the most appropriate method of treatment. The reliability of the diagnosis can be increased by systematically appending additional information to a basic fracture classification. Classification is best carried out on a morphological basis, whereby a descriptor of bone quality can be added in order to introduce the degree of osteoporosis into the decision-making algorithm. Any classification system that claims to provide both treatment and prognosis is inappropriate, because prognosis will depend hopefully on the treatment. Approaches to treatment differ widely amongst centers and surgeons. It is still unclear as to what would be the optimal treatment. Factors such as the individual's functional requirements and ability to cooperate should be given careful consideration. At our institution, hemiarthroplasty is the method of choice for ischemic humeral heads and/or when anatomic reconstruction cannot be obtained. In all other displaced fractures, the main objective is preservation of the head since the best functional results can generally be obtained with internal fixation. Selection of a balanced osteosynthesis, adapted to the weak bone, is mandatory. Bulky, stiff implants are inadequate and may cause additional damage. Load sharing, not load bearing, compound constructions are the aim. Obtaining metaphyseal elastic buttressing is the key element in achieving the necessary load-sharing fixation. The system should allow controlled impaction and be forgiving towards occasional load peaks that will occur and are beyond patient control. Thin and flexible implants are required to realize this type of fixation. Given the polypragmatic approach that is current in clinical practice there is room for further improvement of techniques and implants.

Distal humerus fractures in elderly patients: results after open reduction and internal fixation

Abstract: Problem: Fractures of the distal humerus are difficult to treat. In elderly patients, diminished bone mineral quality and increased trauma-associated joint destruction may make stable joint reconstruction even more problematic. Furthermore, comorbidities and poor tolerance of joint immobilization might be additional factors which influence elbow function negatively. Until now, disagreement has existed on how to treat these fractures in elderly patients. Recommendations range from conservative treatment to primary total elbow replacement. So far, reports in the literature on whether or not open reduction and internal fixation in these patients is justified are very rare. Aim of the study: To analyze fracture patterns, surgical approach, complications, and functional results after open reduction and internal fixation in patients of age 60 years and older. Patients and methods: Retrospective clinical study of two university level 1 trauma centers, including 45 patients (median age 73 years; range, 61–92 years) with surgically treated distal humerus fractures. Fracture patterns were recorded according to their AO classification. All patients were treated by open reduction and internal fixation. A clinical and radiological follow-up was obtained after a minimum of 24 months following surgery (median 87 months; range, 24–121 months). Functional results were evaluated according to the Mayo Elbow Score. Results: Fractures with complete joint involvement were seen most often. Taking the fracture type into consideration, functional results deteriorated with degree of joint involvement. Postoperative complication rate was high, predominantly seen as screw loosening and/or implant failure at the lateral column. Neverthless, functional results were preponderating good or excellent. Factors negatively influencing outcome were joint immobilization longer than 14 days and severe joint involvement. Discussion: In elderly patients, distal humerus fractures, which are often considered “osteoporotic fractures,” still remain one of the most demanding challenges in trauma surgery. The present study demonstrates that despite diminished bone quality and a high complication rate, open reduction and internal fixation in elderly patients is justified. Conclusion: Open reduction and internal fixation of distal humerus fractures in elderly patients should be the main goal, since good elbow function can be achieved in the majority of patients. Elbow immobilization longer than 14 days should be avoided. Stable implant anchorage at the lateral column remains problematic, reflecting a general potential for further implant improvements.

Osteoporosis is markedly underdiagnosed: a nationwide study from Denmark

Abstract: Aim: To compare the number of patients diagnosed with osteoporosis and osteoporotic fractures in Denmark, with the number of subjects expected to have osteoporosis. Subjects and methods: From the National Hospital Discharge Register, records for all patients diagnosed with osteoporosis and/or with osteoporotic fractures between 1995 and 1999 were retrieved. Based on normal Danish values for BMD, the expected number of subjects aged 50 years or more with osteoporosis according to the WHO definition was calculated. Results: The estimated prevalence of osteoporosis was 40.8% of women aged ≥50 years and 17.7% among men. The expected annual incidence was 58,658/million inhabitants in women ≥50 years of age and 23,648/million in men ≥50 years. However, the observed incidence was only 4,823 and 862/million per year, respectively (8.2% and 3.6% of the expected). In 1999, a total of 34,691 hip, spine, and forearm fractures were reported in subjects ≥50 years, and of these, 18,566 were potentially attributable to osteoporosis (14,240 fractures in women and 4,326 in men equaling 14,976 and 5,297/million per year). Only 0.3% of men ≥50 years were receiving a bisphosphonate, while 2.2% of women received a bisphosphonate or raloxifene. Among women ≥50 years, 27.7% received hormone replacement therapy. Conclusions: Osteoporotic fractures of the hip, spine, and forearm are rather frequent in Denmark, but the diagnosis of osteoporosis is rarely used. It seems that osteoporosis is markedly underdiagnosed and undertreated in Denmark as probably also elsewhere. This may have significant implications for the prevention of osteoporotic fractures.

Higher circulating hsCRP levels are associated with lower bone mineral density in healthy pre- and postmenopausal women: evidence for a link between systemic inflammation and osteoporosis.

Abstract: Factors involved in inflammation are linked with those critical for bone remodeling. We examined the association between serum high sensitivity C-reactive protein (hsCRP) levels and bone mineral density (BMD) in healthy women. Serum concentrations of hsCRP and total alkaline phosphatase (ALP) were measured in premenopausal ( n =3,662) and postmenopausal ( n =1,031) women aged 30 years or older. BMD was measured at the femoral neck and lumbar spine using dual energy X-ray absorptiometry. According to the WHO definition, osteopenia was diagnosed at –2.5< T -score <–1.0 SD, and osteoporosis was diagnosed at T -score ≤–2.5 SD at any sites. Compared with normal subjects, log-transformed serum hsCRP levels were higher in osteopenic and osteoporotic subjects (all, P <0.001) with linearity ( P for trend <0.001), after adjustment for age, BMI and menopausal status. Menopausal status did not have a significant interaction on the association ( P =0.457). In both premenopausal and postmenopausal women, serum total ALP levels were higher in the subjects with higher hsCRP quintiles than those with the lowest quintile (all, P for trend <0.001). Multivariate-adjusted odds ratio (OR) for osteoporosis and osteopenia were 1.35 (95% CI, 1.08 to 1.68) in the highest hsCRP quintile of premenopausal women, and OR for osteoporosis was 1.54 (95% CI, 1.10 to 2.53) in the highest hsCRP quintile of postmenopausal women. These findings suggest that subclinical systemic inflammation may be associated with bone turnover rate and bone mass in healthy women.

Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus

Abstract: Bone density, bone turnover and fracture susceptibility were evaluated in 1,132 randomly recruited women, all 75 years old. Seventy-four of the women had diabetes, while 1,058 women did not. Areal bone mineral density (aBMD) of the hip and lumbar spine was investigated by dual energy X-ray absorptiometry (DXA), and bone mass of the calcaneus was measured by ultrasound. Urinary deoxypyridinoline/creatinine (U-DPD/Crea) and serum C-terminal cross-linked telopeptide of type 1 collagen (S-CTX) were assessed as markers of bone resorption. Serum bone-specific alkaline phosphatase (S-bone ALP) and serum osteocalcin (S-OC) were assessed as markers of bone formation. Also, serum 25(OH) vitamin D and serum parathyroid hormone (S-PTH) were assessed. Fracture susceptibility was evaluated retrospectively and prospectively for up to 6.5 years. In diabetic women, the aBMD of the femoral neck was 11% higher (p<0.001), and BMD of the lumbar spine was 8% higher (p=0.002) than in non-diabetic women. There was no difference in bone mass by ultrasound of the calcaneus. Women with diabetes had higher BMD of the femoral neck (p<0.001) and lumbar spine (p=0.03) also after correction for differences in body weight. In diabetic women, U-DPD/Crea, S-CTX, and S-OC were decreased when compared with non-diabetic women (p=0.001 or less). After correction for covariance of body weight and plasma creatinine, S-CTX (p<0.001) and S-OC (p<0.001) were still lower in the diabetic women. Diabetic patients had hypovitaminosis D (p=0.008), a difference explained by differences in time spent outdoors and body weight. S-PTH did not differ between the groups. Women with diabetes had no more lifetime fractures (52%) than women without diabetic disease (57%), (p=0.31). This study shows that elderly women with diabetes and without severe renal insufficiency have high bone mass and low bone turnover. The high bone mass and low bone turnover is not likely to have a strong influence on fracture susceptibility.

Survival after hip fracture

Abstract: Although it is known that overall mortality is increased after hip fracture, the influence of hip fracture risk factors on the subsequent mortality and cause of death has not been well studied. The objective of this study was to establish the survival after hip fracture in women and to assess the impact of comorbidity on mortality. We identified a complete population-based set of 2,245 incident hip fracture cases and 4,035 randomly selected population-based controls among women 50-81 years old in Sweden and followed these subjects for an average of 5 years through the Swedish National Inpatient and Cause-of-Death Registers. Information on factors related to hip fracture was obtained through linkage to hospital discharge data and through a mailed questionnaire. We studied excess mortality of hip fracture patients compared to controls using survival curves and proportional hazard regression models. During follow-up, 896 hip fracture patients (40%) and 516 (13%) controls died. The relative risk (RR) of death, adjusted for age and previous hospitalization for serious disease, was 2.3 (95% CI 2.0-2.5). Although the highest mortality risks were in the 1st 6 months post-fracture, RRs for fractures versus controls were increased for at least 6 years. Increased mortality was apparent both in those with evidence of comorbidity and those without. Hip fracture patients have a substantially increased risk of death that persists for at least 6 years post-fracture. The relative excess mortality is independent of comorbidity and known hip fracture risk factors.

Strontium ranelate: a novel mode of action optimizing bone formation and resorption.

Abstract: Strontium ranelate has been shown to decrease the risk of fractures in postmenopausal women. Its efficacy in clinical studies results from its unique mode of action, on both bone resorption and bone formation. Pharmacological studies in animals have shown that strontium ranelate decreases bone resorption and increases bone formation, resulting in increased bone mass. In ovariectomized rats, strontium ranelate prevented the reduction in bone mineral content and the decrease in trabecular bone volume induced by estrogen deficiency. In this model, strontium ranelate decreased bone resorption, whereas bone formation was maintained at a high level as documented by plasma biochemical markers and histomorphometric indices of bone formation. In the model of osteopenia induced by hind-limb immobilization in rats, strontium ranelate reduced histomorphometric parameters of bone resorption and partially prevented long-bone loss, as assessed by bone mineral content, bone volume, and biochemical indices of bone resorption. In intact mice, strontium ranelate increased bone formation and vertebral bone mass. In intact growing rats, strontium ranelate increased the bone trabecular volume without alteration of mineralization. The unique mode of action of strontium ranelate on bone formation and resorption was supported by in vitro studies. In rat calvaria culture systems and rat osteoblastic cell cultures, strontium ranelate enhanced preosteoblastic cell replication and increased collagen synthesis by osteoblasts. Moreover, strontium ranelate decreased bone resorption in organ cultures and decreased the resorbing activity of isolated mouse osteoclasts. The assessment of bone markers in a clinical trial [Spinal Osteoporosis Therapeutic Intervention (SOTI)] supports the mode of action of strontium ranelate: bone alkaline phosphatase levels increased and C-telopeptide of type I collagen levels decreased in treated patients compared with the placebo group at all time points. Thus, pharmacological and clinical studies suggest that strontium ranelate optimizes bone resorption and bone formation, resulting in increased bone mass, which may be of great value in the treatment of osteoporosis.

The human cost of fracture.

Abstract: In this population-based, observational study, we document the personal burden of fracture and utilization of community and health services for women during the 12-month period following a fracture. Participants were 598 women (aged 35-92 years) with incident fracture in the years 1994-1996 who were enrolled in the Geelong Osteoporosis Study. Almost all hip fracture cases and 27% of nonhip fracture cases were hospitalized. Homes were modified in 14% of cases, and 32% of the women purchased or hired equipment to assist with activities of daily living. Three-quarters of women with hip, pelvis, or lower limb fractures were confined to the home, had to walk with a walking aid, or could walk only short distances for several weeks. After a year, nearly one-half had not regained prefracture mobility. One-seventh of women with upper-limb fractures did not venture outside the home for at least 6 weeks. Nearly half of all fracture cases needed help with personal care and housework during the first 6 weeks. After 6 months, 3.4% of all patients and 19.6% of hip, 12.8% of humeral, and 4.7% of spine fracture patients required assistance with bathing and showering. After a year, more than half of the hip fracture cases remained restricted regarding housework, gardening, and transport. These findings have important implications for rehabilitation therapy. A fracture, regardless of site, had a major impact on a woman's lifestyle and well-being. Most women were restricted in their activities of daily living and suffered loss of confidence and independence. Short-term morbidity was common for all fractures, with varying degrees of prolonged morbidity often extending to at least a year postfracture.

Comparison of mineral quality and quantity in iliac crest biopsies from high- and low-turnover osteoporosis: an FT-IR microspectroscopic investigation.

Abstract: Fourier-transform infrared microspectroscopy (FTIRM) allows analysis of mineral content, mineral crystal maturity and mineral composition at approximately 10-micron spatial resolution. Previous FTIRM analyses comparing 4-micron thick sections from non-decalcified iliac crest biopsies from women with post-menopausal osteoporosis, as contrasted with iliac crest tissue from individuals without evidence of metabolic bone disease, demonstrated significant differences in average mineral content (decreased in osteoporosis) and mineral crystal size/perfection (increased in osteoporosis). More importantly, these parameters, which vary throughout the tissue in relation to the tissue age in healthy bone, showed no such variation in bone biopsies from patients with osteoporosis. The present study compares the spatial and temporal variation in mineral quantity and properties in trabecular bone in high- and low-turnover osteoporosis. Specifically, six biopsies from women (n=5) and one man with high-turnover osteoporosis (age range 39-77) and four women and two men with low turnover osteoporosis (age range 37-63) were compared to ten "normal" biopsies from three men and seven woman (age range: 27-69). "High turnover" was defined as the presence of increased resorptive surface, higher than normal numbers of osteoclasts and greater than or equal to normal osteoblastic activity. "Low turnover" was defined as lower than normal resorptive surface, decreased osteoclast number and less than normal osteoblastic activity. Comparing variations in FTIR-derived values for each of the parameters measured at the surfaces of the trabecular bone to the maximum value observed in multiple trabeculae from each person, the high-turnover samples showed little change in the mineral: matrix ratio, carbonate: amide I ratio, crystallinity and acid phosphate content. The low-turnover samples also showed little change in these parameters, but in contrast to the high-turnover samples, the low-turnover samples showed a slight increase in these parameters, indicative of retarded, but existent resorption and formation. These data indicate that FTIR microspectroscopy can provide quantitative information on mineral changes in osteoporosis that are consistent with proposed mechanisms of bone loss.

Bone mineral density in men with genetic hemochromatosis and HFE gene mutation

Abstract: Genetic hemochromatosis (GH) is an iron overload disorder mainly due to the C282Y mutation of the HFE gene. The possibility of bone involvement was only recently recognized. The aims of this study were to assess bone mineral density (BMD) and bone remodeling in men with GH, and to examine the influence of iron overload. Thirty-eight men (mean age 47.2+/-9.4 years) with well-defined HFE-related GH were studied. They had an important iron overload with liver iron concentration to age ratio >2.5, no previous venesection therapy and were C282Y homozygotes (n=37) or compound C282Y/H63D heterozygote (n=1). BMD measured by DXA was 0.925+/-0.15 g/cm2 at the lumbar spine (LS) and 0.778+/-0.13 g/cm2 at the femoral neck (FN). Osteopenia (T-score<-1 SD) was observed in 78.9% of patients and osteoporosis (T-score<-2.5 SD) in 34.2%. Vitamin D levels were normal, and no 1-84 parathyroid hormone dysfunction was found. Hypogonadism was found in only 13.2% of patients. Patients with hypogonadism had lower LS BMD than eugonadal patients (0.788+/-0.16 and 0.954+/-0.14 g/cm2). Bone remodeling and parathyroid hormone levels were lower in patients with cirrhosis, but BMD values were similar to those in patients without cirrhosis. FN BMD appeared to fall with rising hepatic iron concentrations (r=-0.399). We conclude that there is significant bone loss in HFE-related hemochromatosis that cannot solely be explained by hypogonadism or cirrhosis. Further investigations are needed to determine the role of iron overload itself.

Effects of high-impact exercise on bone mineral density: a randomized controlled trial in premenopausal women.

Abstract: Introduction: The purpose of this randomized controlled study was to assess the effects of high-impact exercise on the bone mineral density (BMD) of premenopausal women at the population level. Materials and methods: The study population consisted of a random population-based sample of 120 women from a cohort of 5,161 women, aged 35 to 40 years. They were randomly assigned to either an exercise or control group. The exercise regimen consisted of supervised, progressive high-impact exercises three times per week and an additional home program for 12 months. BMD was measured on the lumbar spine (L1–L4), proximal femur, and distal forearm, by dual-energy X-ray absorptiometry at baseline and after 12 months. Calcaneal bone was measured using quantitative ultrasound. Results: Thirty-nine women (65%) in the exercise group and 41 women (68%) in the control group completed the study. The exercise group demonstrated significant change compared with the control group in femoral neck BMD (1.1% vs −0.4%; p=0.003), intertrochanteric BMD (0.8% vs −0.2%; p=0.029), and total femoral BMD (0.1% vs −0.3%; p=0.006). No exercise-induced effects were found in the total lumbar BMD or in the lumbar vertebrae L2–L4. Instead, L1 BMD (2.2% vs −0.4%; p=0.002) increased significantly more in the exercise group than in the control group. Calcaneal broadband ultrasound attenuation showed also a significant change in the exercise group compared with the control group (7.3% vs −0.6%; p=0.015). The changes were also significant within the exercise group, but not within the control group. There were no significant differences between or within the groups in the distal forearm. Conclusions: This study indicates that high-impact exercise is effective in improving bone mineral density in the lumbar spine and upper femur in premenopausal women, and the results of the study may be generalized at the population level. This type of training may be an efficient, safe, and inexpensive way to prevent osteoporosis later in life.

Identification of vertebral fractures: an update.

Abstract: Osteoporotic vertebral fracture is associated with increased morbidity and mortality As a powerful predictor of future fracture risk, the identification of vertebral fracture helps target individuals who will benefit from anti-fracture therapy The identification of vertebral fractures is problematic because (1) "normal" radiological appearances in the spine vary greatly both among and within individuals; (2) "normal" vertebrae may exhibit misleading radiological appearances due to radiographic projection error; and (3) "abnormal" appearances due to non-fracture deformities and normal variants are common, but can be difficult to differentiate from true vertebral fracture Various methods of vertebral fracture definition have been proposed, but there is no agreed gold standard Quantitative methods of vertebral fracture definition are objective and reproducible, but the major limitation of these methods is their inability to differentiate between vertebral deformity and vertebral fracture The qualitative visual approach draws on the expertise of the reader, but it is a subjective method with poor interobserver agreement Semiquantitative assessment of vertebral fracture is a standardized visual method, which is commonly applied in research studies as a surrogate gold standard This method is more objective and reproducible than a purely qualitative approach, but can be difficult to apply The established methods focus primarily on the identification of "reduced" or short vertebral height as an indication of vertebral fracture, but this is also a feature of some non-fracture deformities and normal variants A modified visual approach known as algorithm-based qualitative assessment of vertebral fracture (ABQ) has recently been introduced, and this focuses on radiological evidence of change at the vertebral endplate as the primary indicator of fracture Preliminary testing of the ABQ method has produced promising results, but the method requires further evaluation Vertebral imaging by means of dual energy X-ray absorptiometry (DXA) scanner produces images of near-radiographic quality at a fraction of the radiation dose incurred by conventional radiography There is growing interest in vertebral fracture assessment using this technique as a means of assessing a patient's fracture risk Given the increasing availability of new technology and the importance of accurate diagnosis of vertebral fracture, there is an urgent need for better awareness of and training in the definition of vertebral fracture Methods of vertebral fracture definition should be validated by testing the association with clinical outcomes of vertebral fracture, in particular the prediction of incident fractures

Green tea catechin enhances osteogenesis in a bone marrow mesenchymal stem cell line.

Abstract: Green tea has been reported to possess antioxidant, antitumorigenic, and antibacterial qualities that regulate the endocrine system. Previous epidemiological studies found that the bone mineral density (BMD) of postmenopausal women with a habit of tea drinking was higher than that of women without habitual tea consumption. However, the effects of green tea catechins on osteogenic function have rarely been investigated. In this study, we tested (-)-epigallocatechin-3-gallate (EGCG), one of the green tea catechins, on cell proliferation, the mRNA expressions of relevant osteogenic markers, alkaline phosphatase (ALP) activity and mineralization. In a murine bone marrow mesenchymal stem cell line, D1, the mRNA expressions of core binding factors a1 (Cbfa1/Runx2), osterix, osteocalcin, ALP increased after 48 h of EGCG treatment. ALP activity was also significantly augmented upon EGCG treatment for 4 days, 7 days and 14 days. Furthermore, mineralizations assayed by Alizarin Red S and von Kossa stain were enhanced after EGCG treatment for 2-4 weeks in D1 cell cultures. However, a 24-h treatment of EGCG inhibited thymidine incorporation of D1 cells. These results demonstrated that long-term treatment of EGCG increases the expressions of osteogenic genes, elevates ALP activity and eventually stimulates mineralization, in spite of its inhibitory effect on proliferation. This finding suggests that the stimulatory effects of EGCG on osteogenesis of mesenchymal stem cells may be one of the mechanisms that allow tea drinkers to possess higher BMD.

Determinants of vitamin D status in older women living in a subtropical climate.

Abstract: Studies performed in the Northern Hemisphere and in areas distant from the equator have demonstrated significant seasonal variation in 25-hydroxyvitamin D (25OHD) levels. Whether such variation occurs in a subtropical area such as Australasia is not clear. We performed a cross-sectional study of 1,606 healthy, postmenopausal women recruited over a 33-month period. The study had three goals: to determine the normal levels of 25OHD in healthy postmenopausal women living in Auckland, New Zealand; to determine whether seasonal variation of 25OHD occurs at this latitude; to assess the relationship between 25OHD, biochemical indices, anthropometric variables and bone mineral density (BMD). We found significant seasonal variation in 25OHD levels, with the change in monthly ultraviolet dose from summer to winter being followed 6-8 weeks later by a corresponding change in 25OHD levels. Vitamin D insufficiency (25OHD <50 nmol/l) was common. During summer, 28-58% of participants had suboptimal vitamin D status, while in winter, the frequency increased to 56-74%. 25OHD levels correlated with participants' age (r=-0.15), weight (r=-0.11), body mass index (r=-0.13), fat mass (r=-0.14), percentage body fat (r=-0.16), physical activity (r=0.10) and the month of blood sampling (all P<0.0001). Collectively, age, fat mass, physical activity, and month of sampling explained 21% of the variance in 25OHD. No significant relationships were noted between 25OHD and BMD at any site. Other variables that showed significant monthly variation were glucose (P=0.002), serum phosphate, alkaline phosphatase, and albumin (all P<0.0001). There was no monthly variation in BMD at the lumbar spine or proximal femur. In conclusion, there is significant seasonal variation in 25OHD levels, even in a subtropical climate. Furthermore, despite generous amounts of sunlight, considerable numbers of women have suboptimal vitamin D status, even in summer. Our findings support the suggestion that vitamin D supplementation should become standard practice in this population of women, particularly during winter.

Incidence and cost of osteoporotic fractures in France during 2001. A methodological approach by the national hospital database.

Abstract: The objective of this study was to describe the hospital incidence rate and the in-patient costs of three peripheral "osteoporotic" fractures (proximal humerus and hip, distal radius and/or ulna) in women and men aged over 45 in France during 2001. Each stay for fracture was selected from the dataset of the French national hospital database in 2001. The incidence rate (CI 95%) was standardized by age and gender according to the last census of the French population (1999). The effect of age and existence of geographical difference in incidence rates has been studied. For each fracture, we described the number of stays, rate of surgical procedure and in-patient costs according to the 2004 French list of cost per diagnosis-related group (2004 Euros); 118,839 fractures were registered during 2001 (61% hip, 28% distal radius and 11% proximal humerus; sex ratio 0.26). The incidence rate for all fracture was 7,567 (7,519-7,615) and 2,312 (2,283-2,341) for 10(6) inhabitants in women and men aged over 45 years, respectively. The incidence increased significantly whatever type of fracture and gender. There were more fracture incidents in the east of France compared to the west and in the south compared to the north, whatever type of fracture in women and only for hip fracture in men. Surgical procedures were performed in 91% of proximal hip fractures, 83% of distal radius fractures and 53% of proximal humerus fractures. The median in-patient costs were 3,786 Euros for the humerus, from 2,363 to 2,574 Euros for the radius and from 8,048 to 8,727 Euros for the hip. The evaluation of the burden of peripheral fractures is possible using national hospital data in France. The incidence of fractures increased with age and is more common in women. Hip fracture with its higher occurrence, rate of procedure and in-patient costs could be used as a marker of osteoporosis for evaluating strategies of management.