Use Of Anti-osteoporotic Drugs Research Articles

Osteosarcopenia and Pain: Do We Have a Way Out?

Osteosarcopenia (OSP) is a geriatric syndrome characterized by the coexistence of osteoporosis and sarcopenia and associated with an increased risk of fragility fractures, disability, and mortality. For patients with this syndrome, musculoskeletal pain represents the most significant challenge since, in addition to limiting the individual's functionality and promoting disability, it has a huge psychological burden involving anxiety, depression, and social withdrawal. Unfortunately, the molecular mechanisms involved in the development and persistence of pain in OSP have not yet been fully elucidated, although immune cells are known to play a key role in these processes. Indeed, they release several molecules that promote persistent inflammation and nociceptive stimulation, resulting in the gating of ion channels responsible for the generation and propagation of the noxious stimulus. The adoption of countermeasures to counteract the OSP progression and reduce the algic component appears to be necessary, providing patients with a better quality of life and greater adherence to treatment. In addition, the development of multimodal therapies, based on an interdisciplinary approach, appears to be crucial, combining the use of anti-osteoporotic drugs with an educational programme, regular physical activity, and proper nutrition to eliminate risk factors. Based on this evidence, we conducted a narrative review using the PubMed and Google Scholar search engines to summarize the current knowledge on the molecular mechanisms involved in the pain development in OSP and the potential countermeasures to be taken. The lack of studies addressing this topic highlights the need to conduct new research into the resolution of an ever-expanding social problem.

The Nutraceutical Genistein-Lycopene Combination Improves Bone Damage Induced by Glucocorticoids by Stimulating the Osteoblast Formation Process.

Chronic glucocorticoid (GC) therapy is the most common cause of iatrogenic osteoporosis and represents an important risk factor for osteoporosis and bone fractures. New therapeutic approaches are required in order to treat osteoporosis and reduce the side effects related to the use of anti-osteoporotic drugs. In this context, previous studies reported the efficacy of some isoflavones and carotenoids, such as lycopene and genistein, on the reduction of the risk of fracture related to osteoporosis. The aim of this study was to investigate the effects of a combined oral treatment, consisting of genistein and lycopene, in an experimental model of glucocorticoid-induced osteoporosis (GIO). GIO was induced by subcutaneous injection of methylprednisolone (MP, 30 mg/kg) for 60 days, whereas the control group (Sham) received saline solution only. Following induction, MP animals randomly were assigned to receive alendronate, genistein, lycopene, or the association of genistein and lycopene or saline solution for additional 60 days together with MP. Femurs obtained from the Sham group were used for osteoblasts extraction; they were then incubated with dexamethasone (DEX) for 24 h to be then treated with lycopene or genistein or the association of lycopene and genistein for an additional 24 h. Treatments with lycopene and genistein restored the impaired mineralization of cells observed following DEX treatment and stimulated osteoblast differentiation by increasing the depressed expression of bALP and RUNX2 (p < 0.0001). Wnt5a, β-catenin, and Nrf-2 expression were significantly increased following genistein and lycopene treatment (p < 0.0001), thus confirming their antioxidant activity as well as their ability in stimulating osteoblast function, mostly when genistein and lycopene were used in association. The combined treatment of genistein and lycopene improved the bone damage induced by glucocorticoids and significantly restored the normal architecture of bones as well as adequate interconnectivity of bone trabeculae, thus increasing bone mineral density parameters. The obtained data demonstrated that genistein and lycopene but in particular their association might prevent GC’s adverse effects, thus stimulating bone formation and reducing bone resorption, improving bone structure and microarchitecture, through different molecular pathways, such as the Wnt/β-catenin and the Nrf-2 signaling.

Bone fragility: conceptual framework, therapeutic implications, and COVID-19-related issues.

Bone fragility is the susceptibility to fracture even for common loads because of structural, architectural, or material alterations of bone tissue that result in poor bone strength. In osteoporosis, quantitative and qualitative changes in density, geometry, and micro-architecture modify the internal stress state predisposing to fragility fractures. Bone fragility substantially depends on the structural behavior related to the size and shape of the bone characterized by different responses in the load–deformation curve and on the material behavior that reflects the intrinsic material properties of the bone itself, such as yield and fatigue. From a clinical perspective, the measurement of bone density by DXA remains the gold standard for defining the risk of fragility fracture in all population groups. However, non-quantitative parameters, such as macro-architecture, geometry, tissue material properties, and microcracks accumulation can modify the bone’s mechanical strength. This review provides an overview of the role of different contributors to bone fragility and how these factors might be influenced by the use of anti-osteoporotic drugs and by the COVID-19 pandemic.

Initiation of anti-osteoporotic drugs in high-risk female patients starting glucocorticoid treatment: a population study in Norway

SummaryGlucocorticoid use is a risk factor for osteoporosis and fractures. We studied whether women initiating glucocorticoid treatment also started anti-osteoporotic treatment, according to clinical guidelines. Women with versus without previous fracture were twice as likely to start anti-osteoporotic treatment within 1 year after initiating glucocorticoid treatment, but the cumulative incidences were low 9.1% vs. 4.6%, respectively.PurposeUse of glucocorticoids (GC) is a risk factor for osteoporosis and fractures, and clinical guidelines suggest that preventive treatment with anti-osteoporotic drugs (AOD) should be considered when starting GC. Women with high risk of osteoporosis comprise those with previous fractures or a known inflammatory rheumatic disease, for whom the indication of AOD is even stronger. The purpose of these analyses was to investigate whether women initiating GC treatment also started AOD, especially those with high risk of osteoporosis.MethodsWe used data from the Norwegian Prescription Database to identify all women 55 years and older initiating GC treatment in Norway during 2010–2016 and to obtain information on use of AOD. Data from the Norwegian Patient Registry were used to obtain information on previous fractures and diagnoses.ResultsAmong 105,477 women initiating GC treatment during 2010–2016, 3256 had started AOD and 79,638 had discontinued GC treatment after 1-year follow-up. Cumulative incidence of starting AOD after 1 year was 9.1% (95% CI: 7.9, 10.4) for women with vs. 4.6% (95% CI: 4.4%, 4.8%) for women without a previous fracture. Women with rheumatoid arthritis or another inflammatory rheumatic disease were more likely to start AOD than women with other indications. For the whole cohort, the probability of starting AOD treatment within 1 year after initiating GC increased on average 3% per year (HR = 1.03, CI: 1.01, 1.05) from 2010 to 2016.ConclusionsHaving had a previous fracture or an inflammatory rheumatic disease increased the probability of treatment with AOD. However, the proportions starting AOD were much lower than clinically indicated.

Proton pump inhibitors and fracture risk. The HUNT study, Norway.

Proton pump inhibitors (PPIs) are widely prescribed and have been linked to increased risk of fracture. We used data from the Nord-Trøndelag Health Study (HUNT3), The Fracture registry in Nord-Trøndelag, and the Norwegian Prescription Database, including 15,017 women and 13,241 men aged 50-85 years. The study population was followed from the date of participating in HUNT3 (2006-2008) until the date of first fracture (forearm or hip), death, or end of study (31 December 2012). The Cox proportional hazards model with time-dependent exposure to PPIs was applied, and each individual was considered as unexposed until the first prescriptions was filled. To be included, the prescription of PPIs should minimum be equivalent to 90 defined daily doses (DDD) in the period. Individuals were defined as exposed until 6 months after end of drug supply. The proportion of women and men using PPIs was 17.9% and 15.5%, respectively. During a median of 5.2 years follow-up, 266 women and 134 men had a first hip fracture and 662 women and 127 men, a first forearm fracture. The combined rate/1000 patient-years for forearm and hip fractures in women was 49.2 for users of PPIs compared with 64.1 among non-users; for men 18.6 and 19.8, respectively. The hazard ratios with 95% confidence interval for the first forearm or hip fracture among users of PPIs in the age-adjusted analysis were 0.82 (0.67-1.01) for women and 1.05 (0.72-1.52) for men. Adjusting for age, use of anti-osteoporotic drugs, and FRAX, the HR declined to 0.80 (0.65-0.98) in women and 1.00 (0.69-1.45) in men. Use of PPIs was not associated with an increased risk of fractures.

Use of antiosteoporotic drugs and calcium/vitamin D in patients with fragility fractures: impact on re-fracture and mortality risk.

To evaluate the impact of pharmacological treatment in osteoporosis patients with recent fracture and to assess the incidence of subsequent fracture and all-cause mortality. This observational retrospective study was based on data from administrative databases of five Italian Local Health Units. Osteoporosis patients aged ≥ 50 years with hospitalization for vertebral or hip fracture occurring between 01/01/2011 and 31/12/2015 were included. Treatment adherence was calculated using the medication possession ratio. Multivariable proportional hazard Cox model was used to identify factors associated with time to re-fracture and all-cause mortality. A cohort of 3475 patients were included and 41.5% of them did not receive any specific anti-fracture treatment. Among treated patients (N = 2032), the majority (83.6%) received calcium/vitamin D supplementation. Over a mean follow-up of 3 years, the risk of subsequent fractures was 44.4% lower in treated patients compared to untreated ones (HR = 0.556, 95% CI = 0.420-0.735, p < 0.001) and 64.4% lower in those receiving calcium/vitamin D supplementation compared to osteoporosis treatment only (HR = 0.356, 95% CI = 0.237-0.533, p < 0.001). The risk of re-fracture was 77.2% lower in treated patients who were adherent to medication (HR = 0.228, 95% CI = 0.139-0.376, p < 0.001). Treated patients had 64% lower mortality risk over the follow-up compared to untreated ones (HR = 0.360, 95% CI = 0.310-0.418, p < 0.001). A consistent proportion of osteoporosis patients did not receive specific treatment after a fracture, showing poor adherence to national guidelines on osteoporosis treatment. Osteoporosis drug treatment, and to a greater extent in combination with calcium/vitamin D, and adherence were correlated with lower risk of both re-fracture and all-cause mortality.

THE PLACE OF STRONTIUM RANELATE IN THE TREATMENT OF PATIENTS WITH OSTEOPOROSIS (RESULTS OF THE MARC PROGRAM)

Strontium ranelate (SR) that has a proven efficacy in reducing the risk of fractures and in increasing bone mineral density is currently recommended as a second choice drug for the treatment of severe osteoporosis (OP) in postmenopausal women and elderly men. Subjects and methods. In 2014–2015, a survey within the framework of the MARC program (The Use of Antiosteoporotic Drugs in Real Clinical Practice) was conducted in 1799 OP patients aged 25 to 92 years, who had been treated for this disease for at least one year. Among the respondents, there were 1696 people aged 50 years and older (mean age, 64±7 years; disease duration, 2.7±2.4 years) (86% women and 14% men) who were the subjects of this survey. Adherence to performed antiosteoporotic therapy was evaluated within the last 12 months before the survey by the following parameters: which drug had been taken; the number of packages used, treatment gaps and compliance with the treatment regimen. Results and discussion. The survey of the patients included in the study showed that 19% of them had received SR at any time over the course of the disease, and 8% had taken the drug within the year preceding the survey. Thus, SR remains a popular drug in real clinical practice for the treatment of severe OP in patients with no history of coronary heart disease, uncontrolled hypertension, cerebrovascular diseases, peripheral artery disease, and a predisposition to thrombosis and thromboembolism.

Anti-osteoporosis drug use: too little, too much, or just right? The HUNT study, Norway.

To examine the use of anti-osteoporotic drugs (AODs) and to identify predictors for prescriptions. Data were obtained from the Nord-Trøndelag Health Study (HUNT3) performed in 2006-2008 and the Norwegian Prescription Database, including 15,075 women and 13,386 men aged 50-85years. Bone mineral density (BMD) in the femoral neck was measured in a subgroup of 4538 women and 2322 men. High fracture risk was defined as a FRAX score for major osteoporotic fracture (MOF) ≥ 20%; in the subgroup with BMD, high risk was in addition defined as FRAXMOF ≥ 20% or T-score ≤ - 2.5. Hazard ratios (HRs) for predictors of incident use of AODs within 2years after HUNT3 were estimated by Cox' proportional hazards model. Among individuals with FRAX MOF ≥ 20%, 25% of the women and 17% of the men were treated with AODs. Among those with FRAX MOF < 20%, 3% and 1% were treated, respectively. In the subgroup with BMD measurement, 24% of the women and 16% of the men at high risk of fractures were treated, compared to 3 and 1% in women and men not fulfilling the criteria. In women, high age was the strongest predictor for treatment (HR 3.84: 95% confidence interval 2.81-5.24), followed by use of glucocorticoids (GCs) (2.68:1.84-3.89). In men, predictors were use of GCs (5.28: 2.70-10.35) followed by multimorbidity (3.16:1.31-7.63). In the subgroup with BMD, T-score ≤ - 2.5 was the strongest predictor (women 3.98:2.67-5.89; men 13.31:6.17-28.74). This study suggests an undertreatment of AODs in individuals at high risk of fracture.

Effectiveness of anti-osteoporotic drugs to prevent secondary fragility fractures: systematic review and meta-analysis.

Patients with osteoporotic fractures have an increased risk for secondary fractures. However, a rigorous study that assesses the effectiveness of individual osteoporotic drugs in preventing subsequent fractures is lacking. The purpose of this review was to analyze the effectiveness of anti-osteoporotic drugs in preventing secondary fractures. We searched for randomized controlled trials that showed the incidence of secondary fractures while using anti-osteoporotic drugs (bisphosphonates, selective estrogen receptor modulators, parathyroid hormone (PTH), or calcitonin) in MEDLINE, Embase.com , and Cochrane Central Register databases. We estimated risk ratios (RR) and numbers needed to treat (NNT) to prevent secondary fractures. Twenty-six studies met our eligibility criteria. There was a significant reduction in RR (0.38-0.77) after the use of anti-osteoporotic drugs for secondary vertebral fractures. Bisphosphonates and PTH significantly reduced the risk of a secondary non-vertebral fracture (RR 0.59 and 0.64). PTH needed the fewest number of patients to be treated to prevent a secondary vertebral fracture (NNT: 56). Our study demonstrated the effectiveness of anti-osteoporotic agents included in our systematic review in preventing secondary vertebral fractures. Bisphosphonates and PTH were most effective in preventing non-vertebral fractures. We suggest that clinicians should prescribe these drugs to prevent secondary vertebral/non-vertebral fractures.

Diabetes and bone health: latest evidence and clinical implications.

As the prevalence of diabetes is increasing worldwide, research on some of the lesser-known effects, including impaired bone health, are gaining a lot of attention. The two most common forms of diabetes are type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). These two differ in their physiology, with T1DM stemming from an inability to produce insulin, and T2DM involving an insufficient response to the insulin that is produced. This review aims to highlight the most current information regarding diabetes as it relates to bone health. It looks at biochemical changes that characterize diabetic bone; notably increased adiposity, altered bone metabolism, and variations in bone mineral density (BMD). Then several hypotheses are analyzed, concerning how these changes may be detrimental to the highly orchestrated processes that are involved in bone formation and turnover, and ultimately result in the distinguishing features of diabetic bone. The review proceeds by explaining the effects of antidiabetes medications on bone health, then highlighting several ways that diabetes can play a part in other clinical treatment outcomes. With diabetes negatively affecting bone health and creating other clinical problems, and its treatment options potentiating these effects, physicians should consider the use of anti-osteoporotic drugs to supplement standard anti-diabetes medications in patients suffering with diabetic bone loss.

Can anti-osteoporotic therapy reduce adjacent fracture in magnetic resonance imaging-proven acute osteoporotic vertebral fractures?

BackgroundAdjacent fracture of the cemented vertebrae result from crushed fragile trabeculae during follow-up, suggesting impaired bone marrow integrity. This study aimed to determine if anti-osteoporotic therapy can decrease the risk of adjacent fracture in patients after vertebroplasty.MethodsThis retrospective study reviewed of cases of osteoporotic patients with magnetic resonance imaging (MRI)-proven acute vertebral fractures between 2001 and 2007. Osteoporotic patients were investigated as determined by pre-operative MRI with subsequent adjacent fracture of the cemented vertebrae and for the possibility of anti-osteoporotic therapy decreasing the progression of collapse after a minimum of 6 months follow-up. All associated co-morbidities were recorded, as well as the use of anti-osteoporotic drugs (i.e., bisphosphonate, raloxifen, calcitonin, and teriparatide). Cox regression analysis was also performed.ResultsThe 192 vertebral fractured patients who underwent vertebroplasty and anti-osteoporotic therapy had a mean age of 74.40 ± 6.41. The basic characteristics of patients with and without adjacent fracture differed in age, body mass index, rheumatoid arthritis, and use of glucocorticoids and anti-osteoporotic drugs (Table 1). Using the Kaplan-Meier curve, anti-osteoporotic therapy after vertebroplasty had a significant effect on adjacent fracture (p = 0.037, by log rank text). After adjusting for potential confounders, patients with anti-osteoporotic therapy still had a lower adjacent fracture rate than patients without anti-osteoporotic therapy (p = 0.006; HR: 2.137, 95 % CI: 1.1238–3.690). The adjacent fracture rate also increased in old age (p = 0.019; HR: 1.049; 95 % CI:1.008–1.039) and among smokers (p = 0.026; HR: 3.891; 95 % CI: 1.175–12.890).ConclusionsIn this study, adjacent fracture of cemented vertebrae is inevitable after vertebroplasty but can be mitigated by anti-osteoporotic therapy to increase bone mass.

Use of anti-osteoporotic drugs in central Norway after a forearm fracture

Use of anti-osteoporotic drugs (AOD) the first year after a forearm fracture in central Norway was low in the period 2005-2012. Women with fractures used more AOD compared to the general population only in 2006, 2007, and 2011. Female gender, age ≥ 60 years, use of glucocorticosteroids, or ≥ 4 different drugs were associated with AOD use. The primary aim of this study was to examine time trends in prevalence and incidence of AOD use the first year after a forearm fracture from 2005-2012. Further, secondary aims were to investigate if gender, the number of drugs used before fracture, or use of glucocorticoids influenced the prescription of AOD, and to examine adherence to AOD. Data is from the fracture registry in Nord-Trøndelag and the Norwegian Prescription database, including women (N = 1434) and men (N = 513) 40-84years with their first forearm fracture between 2005 and 2012. AOD were defined as bisphosphonates, teriparatide, denosumab, and raloxifene. Prevalence and incidence were calculated, and prevalent use among women with forearm fracture was compared with the population in Nord-Trøndelag and Norway. Age-adjusted Poisson regression analyses for time trends and odds ratio for treatment with AOD was estimated. Adherence was defined as medication possession ratio ≥ 80 %. The first year after the fracture, 11.2% of the women and 2.7% of the men were prevalent users, while 5.1 % and 1.2%, respectively, were incident users of AOD. Bisphosphonates comprised 98.8%. AOD use among women with fractures was significantly higher compared to the general population in Nord-Trøndelag only in 2006, 2007, and 2011. There was a trend towards a decline in AOD use among women with fractures from 2005 to 2012 (coefficient -0.05, p = 0.15). Female gender, age ≥ 60 years, use of glucocorticosteroids, or ≥ 4 different drugs the last year before fracture were associated with AOD use. In women, 54.8% were adherent during 3years after fracture. The use of AOD after a forearm fracture was low. An increased focus on osteoporosis in fracture patients is needed for secondary fracture prevention.

Fracture healing in elderly patients: new challenges for antiosteoporotic drugs

Osteoporosis is a major public health concern, characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fracture. Fracture repair progresses through different pathways, striking a balance between bone formation and bone remodeling mechanisms. Conventionally, fracture repair is divided into defined stages, each characterized by a specific set of cellular and molecular events. In postmenopausal women and elderly patients, bone healing rates are conditioned by cellular and molecular alterations to bone tissue that result in a progressive deterioration of fracture healing ability. In addition, in elderly patients, comorbidities and drugs therapies may also affect fracture healing. For this reason, pharmacological research is now focused on the possible use of antiosteoporotic drugs to promote bone healing in frail patients.

SP0058 Osteoporosis Treatment

Providing that the diagnosis of osteoporosis has been properly done and secondary forms of osteoporosis excluded, the treatment of osteoporosis includes non-pharmocological interventions and the use of anti-osteoporotic drugs with...

Clinical risk factors for osteoporosis are common among elderly people in Nuuk, Greenland

Background. Osteoporosis is a debilitating condition characterized by fractures, pain and premature death. Risk factors for osteoporosis predict the risk of fragility fractures.Aim. To describe the occurrence of risk factors for osteoporosis among populations in Nuuk, the capital of Greenland.Methods. A random sample of women born in 1934–42, 1945–47, 1956, and men born in 1956 were selected from the national civil registry. A questionnaire was sent out in Greenlandic and Danish on risk factors for osteoporosis: family history, smoking habits, alcohol intake, presence of disease, sun exposure, intake of dairy products, age at menopause (women) and number of falls. Additional questions included the frequency of back pain, previous fractures, intake of vitamin D and calcium supplements, use of anti-osteoporotic drugs, steroids and other drugs.Results. The questionnaire was sent to 317 subjects confirmed to be living at an address in Nuuk and 181 (57.1%) responded. More young women than older women were smokers (60.6% vs. 35.0%; p=0.022) while limited sun exposure was reported by more of the old women (37.2% vs. 5.6%; p=0.003). Family history of osteoporosis was reported by 15.0%, without difference between groups. Alcohol and milk intake did not differ between groups. Premature menopause was reported by 17.9% of the women. Falls within the last year were reported by 42.4% with fewer falls in the oldest age group (21.9% vs. 50.0%; p=0.005). Frequency of fragility fractures increased with age (5.7% vs. 24.3% vs. 30.4%; p=0.02) and the risk of a fragility fracture increased with age (p=0.004; OR, 95% CI: 4.5, 1.6–12.2, reference: below 70 years), when adjusted for smoking, gender and falls. The use of anti-osteoporotic drugs was low (3.4%) while 28.8% took calcium and vitamin D supplements.Conclusions. Age is a dominating risk factor for fragility fractures in Greenland. The use of anti-osteoporotic drugs is low in Greenland, even if osteoporotic fractures are common in old age.

Distribution of serum βCTX in a population-based study of postmenopausal women taking into account different anti-osteoporotic therapies (the FRODOS Cohort)

This cross-sectional study evaluated the distribution of serum cross-linked C-telopeptides of collagen type I (βCTXs) in postmenopausal women, the characteristics of bone remodeling, and the factors influencing this bone marker, especially the use of anti-osteoporotic drugs. Women (n=4,175) aged 59-70years randomly selected from the community were invited to participate, measuring βCTXs and lumbar and femoral bone mineral density at recruitment. Risk factors for osteoporosis and the use of anti-osteoporotic treatment were collected with a structured questionnaire. We evaluated the percentage of women with increased (βCTXs >0.620ng/mL) and decreased bone turnover (βCTXs <0.100ng/mL) and those reaching the so-called treatment target (values of βCTXs within the lower half of the reference range for healthy young premenopausal women). Two thousand nine hundred sixty-eight women (70%) participated (2,405 non-treated and 563 treated). Increased and decreased bone turnover was observed in 16.4 and 1.8%, respectively, of non-treated women with significant differences compared with treated women (9.7 and 14.2%, respectively, p<0.001); 28% of non-treated osteoporotic individuals had increased bone turnover versus 14% of osteopenic participants and 8.8% of women with normal bone density (p<0.001). Women receiving bisphosphonates presented the highest percentages of decreased bone turnover (27%) and βCTXs (43%) within the treatment target. Increased bone turnover is observed in 16.4% of non-treated postmenopausal women and is more frequent in individuals with osteoporosis, whereas decreased bone turnover is unusual. Most participants taking bisphosphonates had values within the treatment target, but nearly one quarter had decreased bone turnover.

Vitamin D supplementation is required to normalize serum level of 25OH-vitamin D in older adults: an observational study of 974 hip fracture inpatients.

Vitamin D deficiency is highly prevalent in older adults in all continents. In this study we assessed the vitamin D status of hip fracture subjects across different hospitals in a real word situation using the data from a multicenter cohort study on outcomes in orthogeriatric units. We performed a prospective cohort study on 974 consecutive patients 75 yr or older admitted with fragility hip fracture over a 12 months period at 4 general hospitals of different districts in Emilia Romagna Region, Italy. Data collected included comorbidity, cognitive impairment, prefracture functional status, walking ability, living arrangement along with the use of antiosteoporotic drugs, serum intact PTH and serum 25-hydroxyvitamin D [25(OH)D]. Mean 25(OH)D serum levels were 12.2±9.4 ng/ml and 84.2% of patients had levels below recommended values. Male had a higher probability to have values within the reference range [odds ratio (OR): 1.74 (1.13-2.67); p=0.012] while living in nursing resulted negatively related even if only close to statistical significance [OR: 0.24 (0.06-1.02); p=0.051]. Vitamin D supplementation appeared to be the strongest factor associated with adequate level of vitamin D levels [OR: 4.50 (2.57-7.88); p<0.001). This study confirmed the very high rate of severe vitamin D deficiency in Italian subjects admitted with hip fracture. Our study also showed that supplementation of vitamin D is the strongest determinant influencing serum 25(OH)D level of older persons with hip fracture and these results should be taken into account when planning treatment in older persons.

Post–hip fracture use of prescribed calcium plus vitamin D or vitamin D supplements and antiosteoporotic drugs is associated with lower mortality: A nationwide study in Finland

We previously found a positive association between calcium plus vitamin D and antiosteoporotic drugs and survival among hip fracture patients. Our aim was to verify this observation using a nationwide database. A retrospective cohort of home-discharged hip fracture patients aged 50 years or older (n = 23,615) was enrolled from the national database. Primary exposure was medical treatment for osteoporosis, and the outcome was all-cause mortality. Cumulative mortalities were calculated using the Kaplan-Meier estimator. The relationship between mortality and medication purchases was modeled using Cox's proportional hazards regression with time-dependent covariates for medication use. One in 4 women and 1 in 10 men with a hip fracture were treated for osteoporosis in Finland. Unadjusted 1-year mortality was lower among patients who purchased calcium plus vitamin D or vitamin D supplements and antiosteoporotic drugs than among those who did not purchase these medications [hazard ratio (HR) = 0.74, 95% confidence interval (CI) 0.67-0.81]. The difference in unadjusted cumulative mortality remained in favor of the drug users for at least 5 years. Among men, the use of calcium plus vitamin D or vitamin D supplements was associated with lower 1-year mortality even after adjustments for observed confounders (HR = 0.74, 95% CI 0.56-0.97). Among women, the use of antiosteoporotic drugs was associated with lower mortality (HR = 0.79, 95% CI 0.67-0.93). There was a tendency to even better survival in both genders if calcium plus vitamin D or vitamin D supplements and antiosteoporotic drugs were used simultaneously, the HR being 0.72 (95% CI 0.50-1.03) in men and 0.62 (95% CI 0.50-0.76) in women.

Post-Fracture Prescribed Calcium and Vitamin D Supplements Alone or, in Females, with Concomitant Anti-Osteoporotic Drugs is Associated with Lower Mortality in Elderly Hip Fracture Patients

Several studies have shown excess mortality among hip fracture patients compared with the normal population of the same age. Finnish guidelines for medical treatment of hip fracture patients recommend anti-osteoporosis medication and the daily concomitant use of prescribed calcium and vitamin D supplements. However, whether post-fracture use of calcium and vitamin D supplements is associated with survival in such patients has not been evaluated. To study the association between survival in hip fracture patients and patients' sex and age, pre-fracture vitamin D status, American Society of Anesthesiologists - Physical Status (ASA-PS) class, type of fracture and post-fracture use of prescribed calcium plus vitamin D and anti-osteoporotic medication. The study population was 221 hip fracture patients primarily treated in acute care for a new hip fracture in 2003-4 in two Finnish hospitals. After a median of 27.5 months from the fracture, a questionnaire was sent to all patients who were still alive at the time (n = 137). The patients were queried about their use of prescribed calcium plus vitamin D supplementation and of anti-osteoporotic drugs. The follow-up time for use of anti-osteoporotic medication and prescribed calcium and vitamin D was 19.5-36 months (median 27.5 months). Data on the use of prescribed calcium plus vitamin D supplementation and anti-osteoporotic drugs were checked against information on reimbursement of drug prescriptions held by the Finnish Social Insurance Institution. A total of 4 years' (48 months') survival data for all patients in the study population was also obtained, with the dates of patient deaths being checked against Official National and Regional population statistics. Patient survival was analysed using both the Bayesian multivariate analysis and the life table method. In the multivariate analysis, the combination of variables that best explained post-fracture survival was as follows: age <80 years; ASA-PS class 1-2 (ASA-PS class 1 and 2 data were combined in calculations); post-fracture use of prescribed calcium plus vitamin D supplements concomitantly with anti-osteoporotic drugs; post-fracture use of prescribed calcium plus vitamin D supplements; post-fracture use of anti-osteoporotic drugs only; and type of fracture (femoral neck or subtrochanteric). This model correctly predicted 74% of cases. At 36 months, we observed a 36% reduction in deaths in females who used prescribed calcium plus vitamin D supplementation and a corresponding 43% reduction in males. Survival of females who used anti-osteoporotic drugs concomitantly was even greater (43% reduction in deaths) over the entire follow-up period. Excess mortality was highest in females and males who used neither anti-osteoporotic drugs nor prescribed calcium and vitamin D. Our results indicate a potential relationship between reduced mortality and post-fracture use of prescribed calcium plus vitamin D supplementation and, in females, concomitant use of anti-osteoporotic drugs. However, further investigations are needed to understand the reason for the reduction in the risk of death. Population-based, randomized, placebo-controlled trials with total mortality as the main endpoint should be conducted to verify our results.

Non-Hip Peripheral Osteoporotic Fractures: Epidemiology and Significance

Fractures are the most serious consequence of osteoporosis. Non-vertebral and non-hip fractures are seldom recognised as important, even though they account for the majority of all fractures. The most prevalent localisations are distal radius, proximal humerus, ribs, clavicle, and the pelvis. According to the results from large phase III clinical trials for placebo groups, their incidence ranges from 4.9 % to 12.0 %. Hospital morbidity data in Croatia in 2006 show that peripheral non-hip fractures ranked among the leading fifteen injuries, accounting for 23.7 % of all injuries in patients aged 60 years and above. Risk factors for non-hip and non-vertebral fractures are similar to other osteoporotic fractures, and the main are low bone mineral density and earlier fractures. Quality of life is considerably affected by these fractures, and medical costs are very high, soaring as high as 36.9% of all national medical costs in the USA. Non-vertebral non-hip fractures need more attention, which was also recognised by the European regulatory bodies that approve use of anti-osteoporotic drugs.