Modifiable and non-modifiable risk factors affecting walking recovery after hip fracture.

UNLABELLED: Modifiable and non-modifiable predictors of mobility recovery were analyzed on a sample of 774 hip fracture patients according to pre-fracture abilities. Overall predictors were mostly non-modifiable factors related to frailty of patients with the exception of 25-hydroxyvitamin D concentration which significantly affected walking recovery, especially in patients with higher pre-fracture performance. INTRODUCTION: This study aims to investigate mobility changes after hip fracture with the aim of identifying modifiable and non-modifiable predictors of mobility recovery according to different pre-fracture abilities. METHODS: This is a prospective inception cohort study of consecutive older patients, admitted with a fragility hip fracture in three Hospitals of Emilia Romagna (Italy). A sample of 774 patients alive at the sixth month was divided into three groups according to pre-fracture ambulation ability (group 1: mobile outdoors; group 2: mobile indoors; and group 3: mobile with help). The relationship between baseline characteristics of patients and the odds of walking recovery was analyzed using multivariate regression analysis. RESULTS: Mortality differed significantly among the three groups and was the highest in patients needing help to walk. Among the survivors, only 50.3 % of patients recovered walking ability. In a multivariate analysis, independent risk factors were different among the three groups. In group 1, older age, comorbidities, the use of walking devices before fracture, and low albumin level acted as negative factors while male gender, a pre-fracture high functional status, and higher 25-hydroxyvitamin D levels increased the probability of full recovery. In group 2, only pre-fracture functional status and 25-hydroxyvitamin D concentration were related to the recovery of walking ability. Pre-fracture functional status was also the only significant predictor for patients in group 3. CONCLUSIONS: Several baseline characteristics of patients are related to the likelihood of recovering walking ability after hip fracture. The 25-hydroxyvitamin D level seems to be the only relevant modifiable factor even if the effectiveness of its supplementation has yet to be demonstrated.

Impact of multidisciplinary hip fracture program on timing of surgery in elderly patients.

UNLABELLED: The effect of patient characteristics and organizational and system factors on time to surgery were studied using Emilia Romagna Region database and hospital survey. The results showed that the implementation of a Hip Fracture Program significantly increased the probability of early surgery while single intervention had only slight effect INTRODUCTION: The purpose of this study is to evaluate the effect of formal Hip Fracture Program (HFP) on timing of surgery in hip fracture older patients. METHODS: This is a retrospective cohort study based on Emilia Romagna administrative databases. Data on organizational and system factor were also obtained through a hospital survey. A multilevel logistic regression analysis was carried out to assess the effect of covariates on early surgery, taking into account patient level, hospital level, and trust level variability. RESULTS: From 1 January to 31 December 2011, 5,520 subjects over 65 years old underwent surgical repair for hip fracture in Emilia Romagna. The mean waiting time to surgery was 3.4 ± 12.3 days, and the overall percentage of patients operated within 2 days was 52.2%. In the adjusted multilevel logistic model, significant risk factors affecting the timing of surgical intervention at patient level were age, comorbidity, day of admission, and antiplatelet or warfarin therapy while no significant single variables were found at hospital level including dedicated operation theater, hospital volume, dedicated orthogeriatric beds, and geriatrician involvement. The most significant variable was the implementation of HFP at trust level that increased three times the probability of early surgery after adjusting for confounding variables (OR 3.216, 95% CI 0.582-6.539). CONCLUSIONS: Several modifiable organizational factors may affect the proportion of patients with hip fracture undergoing early surgery. This study suggests that the development and the implementation of an evidence-based HFP at trust level are a key point of the strategy of quality of care.

Identifying a standard set of outcome parameters for the evaluation of orthogeriatric co-management for hip fractures.

BACKGROUND AND PURPOSE: Osteoporotic fractures are an increasing problem in the world due to the ageing of the population. Different models of orthogeriatric co-management are currently in use worldwide. These models differ for instance by the health-care professional who has the responsibility for care in the acute and early rehabilitation phases. There is no international consensus regarding the best model of care and which outcome parameters should be used to evaluate these models. The goal of this project was to identify which outcome parameters and assessment tools should be used to measure and compare outcome changes that can be made by the implementation of orthogeriatric co-management models and to develop recommendations about how and when these outcome parameters should be measured. It was not the purpose of this study to describe items that might have an impact on the outcome but cannot be influenced such as age, co-morbidities and cognitive impairment at admission. METHODS: Based on a review of the literature on existing orthogeriatric co-management evaluation studies, 14 outcome parameters were evaluated and discussed in a 2-day meeting with panellists. These panellists were selected based on research and/or clinical expertise in hip fracture management and a common interest in measuring outcome in hip fracture care. RESULTS: We defined 12 objective and subjective outcome parameters and how they should be measured: mortality, length of stay, time to surgery, complications, re-admission rate, mobility, quality of life, pain, activities of daily living, medication use, place of residence and costs. We could not recommend an appropriate tool to measure patients' satisfaction and falls. We defined the time points at which these outcome parameters should be collected to be at admission and discharge, 30 days, 90 days and 1 year after admission. CONCLUSION: Twelve objective and patient-reported outcome parameters were selected to form a standard set for the measurement of influenceable outcome of patients treated in different models of orthogeriatric co-managed care.

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

BACKGROUND: 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. METHODS: 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]. RESULTS: 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). CONCLUSION: 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.

Uses and misuses of statistics: the case of strontium ranelate and the number needed to treat.

In the last 15 years, several pharmacological agents for the prevention of fractures have been developed and commercialized. Most of them showed to be effective in reducing fracture risk. The enhanced availability of drugs to prevent fractures has generated a fierce competition among pharmaceutical companies to conquer a share of the potential market, often with claims of superiority of a drug over another without direct comparisons. The definitive way to compare different treatments would require randomized head to head trials. These trials are expensive, need large samples and are unlikely to be ever performed. Therefore, it has become a common practice to compare pharmacological agents through observational studies on administrative databases or by the indirect comparison of the results of individual randomised-controlled trials (RCT) and their meta-analyses. These studies may produce evidence of clinical value, complementary to that given by RCT. However, without a proper and complete analysis, they may result in a biased picture of effectiveness and be completely misleading. In this article, we critically disclose how such competition may produce biased and misleading picture of evidence, by reviewing the significance of the number needed to treat, absolute risk reduction and relative risk reduction in relation to vertebral fractures prevention with available drugs.

Assessment of the 10-year risk of fracture in Italian postmenopausal women using FRAX®: a north Italian multicenter study.

The aim of the study was to estimate the absolute risk of fracture in a sample of postmenopausal women with the Italian version of FRAX®, using femoral neck bone mineral density (BMD) and 3 internationally validated clinical risk factors (CRFs) (history of fragility fracture, family history of hip fracture, current smoking). We retrospectively studied 9586 women (mean age 64.1 yr) examined in three osteoporosis centers from Northern Italy over two years (2001-2002). The risk of major osteoporotic (clinical spine, hip, forearm and humerus) and hip fractures was estimated using the online version of the FRAX algorithm adapted for Italy. The median 10-year risk was 7.5% for osteoporotic fracture and 1.7% for hip fracture. 25% of subjects had a 10-year risk ≥ 12.1% for osteoporotic fracture and ≥ 4.1% for hip fracture. The median 10-year risk of fracture increased with the number of prevalent CRFs. For major osteoporotic fractures risk rose from 6.3% to 10.9%, 21.4% and 40.9% with 1, 2 and 3 prevalent CRFs, respectively. For hip fractures the corresponding figures were: 1.3%, 2.7%, 7.0% and 21.9%, respectively. However, it must be emphasized that in 2 out of 3 women, none of the CRFs examined was present and the assessment of risk was limited to age and BMD. Our data provide the first description of the effect of the combination of BMD, age and CRFs on fracture risk stratification in a large sample of Italian postmenopausal women using FRAX®. The results are a useful starting point to define criteria for the application of FRAX® in clinical practice in Italy.

Comprehensive care.

Comprehensive care (CC) represents the basic approach of orthogeriatric comanaged care with the overall objectives of improving results regarding physical and psychological functions and reducing hospitalization, long-term care placement and mortality. It is a two-stage process that includes the Comprehensive Geriatric Assessment (CGA) and the development and implementation of an interdisciplinary treatment plan based on priority interventions and unmet needs. In older hip fracture patients CC has to face crucial issues such as treatment choice and surgical options, clinical stabilization of patients before surgery and the prevention and treatment of complication in the postoperative phase. The main aim are to avoid inappropriate surgical delays and reduce the overall number of days of immobility endorsing an early ambulation with full weight bearing as tolerated. Multiprofessional CC must also ensure uninterrupted care for transition between the different care levels that patients need after fracture before returning home. Therefore another important issue is a structured discharge plan tailored to the individual patient identifying subjects that could benefit from a skilled or more intensive rehabilitation, identifying patients and family that will probably need a higher level of care even after rehabilitation, determining timing of discharge, defining the continuing care that needs to be provided and finally ensuring the patient has access to available services and resources. However, the implementation of a comprehensive and multidisciplinary co-care model in an orthopedic unit is a difficult task because it is necessary a great effort to change cultural attitudes related to traditional model of care.

Optimal setting and care organization in the management of older adults with hip fracture.

Hip fracture (HF) is a common event in the geriatric population and is often associated with significant morbidity, mortality and costs for the Healthcare Systems. The growing awareness of HF consequences and the expected rise in the total number of HF worldwide have led to the development and implementation of models of care alternative to the traditional ones for the acute and post-acute management of HF older adults. These services were set to minimize in-hospital complications, streamline hospital care and provide early discharge with the main objectives of improving functional and clinical outcomes, and reducing healthcare costs associated with hip and other fractures. Basically, the main feature that distinguishes these models is the different healthcare professional that retains the responsibility of the care during the acute and postacute phases. This review has been conceived to provide a brief description of the models implemented in the last twenty years, to describe their potential benefits on short- and long-term outcomes, to define the strengths and limitations of these models and the areas of uncertain, and to make some consideration about the future. Actually, on the basis of available studies, it is not possible to define the best model of care for HF older adults. However, the more complex and sophisticated services, characterized by a multidisciplinary approach demonstrated, in randomized-controlled and before-after observational studies, to produce better outcomes compared to the traditional or simplest models. Further research is warranted to confirm long-term functional and clinical benefits of these models and to evaluate their cost-effectiveness.

High prevalence of secondary hyperparathyroidism due to hypovitaminosis D in hospitalized elderly with and without hip fracture.

OBJECTIVES: To determine and compare the prevalence of secondary hyperparathyroidism (HPTH) in a population of community-dwelling and institutionalized older adults hospitalized with and without hip fracture, and to evaluate factors correlated with secondary HPTH in this population. METHODS: Circulating concentrations of serum intact PTH, 25-hydroxyvitamin D [25(OH)D] total serum calcium and albumin were measured in 160 subjects with an osteoporotic fracture of the proximal femur and in 160 matched controls hospitalized for a disease unrelated to bone status. Patients with secondary causes of bone loss and taking medications affecting bone metabolism were excluded. Age, sex, place of residence and the ability to perform basic activities of daily living (BADL) two weeks before hospital admission were recorded at baseline. RESULTS: Patients were comparable with regard to the baseline demographic, biochemical and functional characteristics. The overall prevalence of secondary hyperparathyroidism was 51.2%, without significant differences between hip fractured patients and controls (50.6 vs 51.9%, p=0.911). In bivariate analysis only the age and functional status (BADL) demonstrated a significant relationship with secondary HPTH, while sex and place of residence were not significant. These results were also confirmed in multivariate analysis. Particularly, the risk of secondary HPTH increased with age and with the number of functions lost in BADL: patients fully dependent showed a 3 times as high risk (odd ratio 3.07, 95% confidence interval 1.73 to 5.46, p=0.000) compared to patients independent in BADL, and subject aged >88 yr had a twice as high risk of developing secondary HPTH compared to younger ones (odd ratio 2.28, 95% confidence interval 1.20 to 4.32, p=0.012). CONCLUSION: These results show that secondary HPTH due to hypovitaminosis D is a frequent disorder in hospitalized elderly, strongly correlated with the functional status, irrespective of sex and place of residence.

Effects of nandrolone decanoate on bone mass in established osteoporosis.

A double-blind, randomized, placebo-controlled study was conducted in 46 postmenopausal women with established osteoporosis in order to assess the long-term effects of nandrolone decanoate on the bone mineral density (BMD) of the lumbar vertebrae and of the distal third of the radius and on the biochemical markers of bone turnover. The patients received intramuscular injections of placebo or 50 mg nandrolone decanoate every 3 weeks for 18 months. Thirty-two of the initial 46 patients completed 1 year of study and 25 completed the whole study period of 18 months. Overall, vertebral BMD increased by 2.9% in the nandrolone decanoate group and fell by 2.3% in the placebo group. Radial BMD showed a slight but transient improvement, with a subsequent return to basal levels in the nandrolone decanoate group, whereas there was a progressive decrease in the placebo group. Patients treated with nandrolone decanoate also complained less of bone pain. Urinary hydroxyproline decreased significantly in treated patients, whereas osteocalcin tended to increase, but the change was not significant. HDL cholesterol concentrations decreased only slightly and haemoglobin increased significantly in the nandrolone decanoate group. Two patients treated with nandrolone decanoate withdrew from the study because of hirsutism and hoarseness. The results indicate that nandrolone decanoate exerts positive effects on vertebral BMD and on bone pain in patients with established postmenopausal osteoporosis.

Effects of chronic heroin abuse on bone and mineral metabolism.

Though the chronic use of opiates can modify several body functions, only a few data are available on the effects of opioid drugs on mineral metabolism. We have examined the possible consequences of chronic opiate abuse on bone mass, bone turnover and calcium metabolism in 13 male chronic heroin users, examined 1-2 days after the last administration of the drug (group A), 14 former male heroin addicts, examined 4-24 months after drug discontinuation (group B), and 22 healthy, age- and sex-matched control subjects. In group A, the vertebral bone mineral density (measured by Dual-Photon Absorptiometry) was significantly lower (p < 0.05) than in the control subjects, despite similar values of total body bone mineral, lean body and fat mass. Blood-ionised calcium and urinary calcium and hydroxyproline were significantly increased (p < 0.01), whereas parathyroid hormone was lower than in controls (p < 0.01). Bone alkaline phosphatase and osteocalcin, however, were not significantly different from the control values. LH and testosterone levels were low (p < 0.01 vs controls). In contrast, group B subjects did not show significant differences from the control group. The chronic abuse of opioid drugs may be associated with altered bone metabolism and reduced trabecular bone mass, attributable, at least in part, to gonadal deficiency. These alterations seem reversible after drug discontinuation.

Hip fracture in Italy: epidemiology and preventive efficacy of bone-active drugs.

In this paper we report the results on the epidemiology of hip fracture and the preventive efficacy of bone-active drugs in Italy, observed in men and women aged 50 years or over, recruited in the three Italian centres participating in the Mediterranean Osteoporosis Study (MEDOS), namely Parma, Rome, and Siena. The number of fractures observed was 1,437 in a catchment area population of 847,508 individuals, with a total incidence of 169.6/100,000--a female-to-male ratio of 3.5 and a doubling-time of about 5.5 years. The female excess becomes evident in the age groups over 60 years. The mean age of fractures was 77 years in females and 73 in males. From the data collected, the estimated number of fractures per year in the Italian population aged over 50 years is 32,000. The pattern of use and the preventive efficacy of bone-active drugs was examined in women. Calcitonin and calcium were the drugs mainly used; less than 3% had taken vitamin D or oestrogen and only a minor percentage had taken anabolic steroids. Fluorides were not used at all. As seen in the European sample, the protective effect of calcium and calcitonin is statistically significant even in Italy, while vitamin D is not. The use of anabolic steroids was associated with a decrease in risk. Oestrogen administration does not seem to reduce the relative risk of hip fracture in Italian women, probably due to the small sample size.

Spontaneous release of interleukin-I and interleukin-6 by peripheral blood mononuclear cells after oophorectomy.

1. We studied the changes in interleukin-1 and interleukin-6 secretion by peripheral blood mononuclear cells from 12 premenopausal women after oophorectomy and seven premenopausal women who had undergone simple hysterectomy. 2. The results showed that 1 month after surgery interleukin-1 secretion increased by 414 +/- 171% (mean +/- SEM) and interleukin-6 secretion increased by 1354 +/- 481% in oophorectomized women, whereas only non-significant fluctuations in the secretion of both cytokines (-9% +/- 29% for interleukin-1 and -31% +/- 19% for interleukin-6) were seen in the women who had undergone simple hysterectomy. The difference between the two groups was significant (P = 0.035 for interleukin-1 and P = 0.003 for interleukin-6). In addition, oophorectomy, but not simple hysterectomy, was followed by significant increases in plasma ionized calcium concentration (P < 0.05), plasma alkaline phosphatase activity (P < 0.01) and plasma osteocalcin concentration (P < 0.02), and a reduction in plasma parathyroid hormone level (P < 0.01). 3. We conclude that ovary ablation may modify cytokine secretion by peripheral blood mononuclear cells. If this phenomenon occurs in the bone microenvironment, it could be important in the loss of bone observed after oophorectomy. However, the possibility of an independent alteration induced by the lack of gonadal hormones but unrelated to bone turnover cannot be excluded.

Longitudinal study of bone loss after thyroidectomy and suppressive thyroxine therapy in premenopausal women.

The effects of suppressive doses of L-thyroxine on the appendicular and axial bone mineral content were followed for 12-36 months after total or subtotal thyroidectomy in 15 premenopausal women. Compared to age-matched controls, these patients had a more marked bone loss of the spinal bone mineral content (2.6 +/- 1.9% vs 0.2 +/- 1.2% per year). The changes in radial cortical bone density were not significantly different from the control group. We conclude that when a suppressive therapy with L-thyroxine is necessary the rate of bone loss should be monitored at regular intervals.

Calcitonin nasal spray reduces opioid withdrawal syndrome without modification of endogenous opioid secretion.

It has been suggested that the well known analgesic effect of calcitonin (CT) may result from an enhanced secretion of opioid peptides. The purpose of this double-blind, controlled study was therefore to evaluate the effectiveness of CT on the opiate withdrawal syndrome. 20 drug addicts were randomly allocated to receive either 200 UI/day of salmon CT (n = 10) or placebo (n = 10) by nasal spray, after the abrupt withdrawal of low-dose methadone (20 mg/day). The severity of the withdrawal syndrome was evaluated by means of a score derived from a symptom check-list. Plasma beta-endorphin, glucose and insulin levels were measured before and after CT administration. The subjects treated with spray CT had significantly lower score than those treated with placebo. Beta-endorphin levels did not show any significant variation in both groups. An inhibitory action of CT on insulin secretion was observed. Our data suggested that CT might be considered a useful supportive measure for opiate withdrawal. CT action does not seem to involve the opioid system, but is probably mediated by a direct action on specific receptors or by a modulation of noradrenergic pathways.

Intermittent treatment with intravenous 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP) in the therapy of postmenopausal osteoporosis.

Since data on the efficacy of 4-amino-2-hydroxybutylidene-1,1-bisphosphonate (AHBuBP) in the therapy of osteoporosis are not yet available, we have examined in an open, randomized study, the effects of an intravenous intermittent treatment with this drug on the vertebral and radial bone mass in postmenopausal osteoporosis. Forty postmenopausal osteoporotic women were randomly assigned to one of two groups, one treated with AHBuBP (5 mg/day on two consecutive days every 3 months for one year; n = 20), the other with oral calcium (n = 20). The bone mineral density (BMD) of the spine increased significantly in women receiving AHBuBP, whereas it tended to decrease in patients given calcium. The differences in the vertebral BMD changes between groups was highly significant (P less than 0.01). Radial BMD tended to increase in patients treated with AHBuBP, and to decrease in patients receiving calcium. The difference in the linear trends was statistically significant (P less than 0.05). The side effects of AHBuBP (a transient acute phase reaction in 3 out of 20 subjects) were slight and well-tolerated. A good effect of AHBuBP was observed also on back pain (P less than 0.05). We conclude that intermittent treatment with AHBuBP is capable of increasing spinal BMD and conserving radial BMD in postmenopausal osteoporosis and may represent a convenient therapeutic choice in this condition.

Impaired prolactin response to hyperthermia in heroin addicts.

The response of PRL, FSH and LH to sauna-induced hyperthermia was examined in 8 male former heroin addicts (studied after 14-24 days of abstinence) and 8 age- and sex-matched control subjects. The basal levels of PRL tended to be higher in former drug users than in control subjects (p = 0.07). After sauna, there were no changes in the addict group, whereas a significant increase was observed in normal subjects (p less than 0.001). Baseline plasma LH and FSH levels were significantly lower in former drug users (p = 0.02), but no change was found after sauna in either group. These findings are consistent with the existence of a deficient adaptation to thermal stress in chronic drug users, even after a relatively short drug-free period.