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A high proportion of patients with fragility fracture, mainly hip fracture, have a variable degree of comorbidity and show some degree of dependence in basic or more complex activities of daily living. Evaluating these patents following the geriatric concept of frailty, about one third of hip fracture patients may be categorised as frail with high risk of poor outcomes and prolonged length of stay, one third as not frail, and about one third with an intermediate condition. Due to the high vulnerability, combined with the hip fracture event and surgical repair procedures, a multidisciplinary approach that includes geriatric competencies becomes essential to improve short and long-term outcomes after hip fracture. A key element of an effective process of care is a true co-managed approach that applies quality standards and provides a fast-track pathway of care, minimises the time the patient spends in bed, and reduces postoperative complications by means of standardised procedures. The occurrence of a fragility fracture is the strongest risk factor for a subsequent fracture. Moreover, frail subjects have a further risk of fracture due to high risk of falls - related to loss of muscle mass, multiple illnesses, impaired balance and weakness. Thus, effective secondary prevention strategies are essential to reduce morbidity and mortality after hip fracture, and they are currently a standard task of orthogeriatric care. Fracture liaison services (FLS) are probably the most efficient way of addressing secondary prevention including the assessment of both bone health and falls risk. Therefore, the optimal management of frail patients with fragility fracture includes both orthogeriatric care and FLS, which are complementary to each other. Orthogeriatric collaboration is also powerful in influencing healthcare policy. British experience as well as that in Ireland, Australia and New Zealand, have shown that when two widely disparate specialisms say the same thing, they may achieve a fundamental shift in attitudes and behaviour of both managers and clinicians. Furthermore, a continuous real-time audit, at national level, is a powerful driver for change and better standards of care.

To investigate the relationship between onset of delirium and time to surgery in hip fracture (HF) patients with a different degree of cognitive impairment. Retrospective analysis of a prospective database of 939 older adults, aged ≥ 75 years admitted with a fragility HF. Subjects underwent a Comprehensive Geriatric Assessment on admission, evaluating health status, prefracture functional status in basic and instrumental activities of daily living, and walking ability. According to the Short Portable Mental Status Questionnaire score, patients were stratified into three categories: cognitively healthy (0–2 errors), mildly to moderately impaired (3–7 errors) and severely impaired (8–10 errors). Time to surgery (from admission) was expressed as days. The occurrence of delirium was ascertained daily by Confusion Assessment Method. Two hundred ninety-two (31.1%) patients experienced delirium during in-hospital stay. They were older, with a higher degree of comorbidity and functional impairment compared to patients without delirium. In multivariate analysis, surgical delay resulted a significant independent risk factor for delirium (HR 1.11, 95% CI 1.01–1.24), along with age, prefracture functional disability and cognitive impairment. When the analysis was performed accounting for the cognitive categories, surgical delay demonstrated to increase the risk of delirium only in the subcategory of mildly to moderately impaired patients, while no significant effect was demonstrated in patients cognitively healthy or severely impaired. The study supports the concept that older adults with HF should undergo surgery quickly. Patients with mild-to-moderate cognitive impairment should be primarily considered as the best target for interventions aiming to reduce time to surgery.

To compare the pathways of care and clinical results for patients admitted for hip fracture (HF) in 3 orthogeriatric co-managed care centers in order to estimate the effect of system factors on mortality and functional outcome.Prospective inception multicenter cohort study.Three tertiary Hospitals.806 patients consecutively admitted with HF.1-Year mortality, the loss of 1 or more functional abilities in activities of daily living (ADLs), and the recovery/maintenance of independent ambulation at 6 months from the fracture.On the whole sample, 71.1% of patients survived 1 year from the fracture. In one hospital the risk of 1-year mortality was significantly higher even after adjusting for age, sex, comorbidity, prefracture functional status and cognitive impairment (odd ratio (OR) 1.56, 95% confidence interval (CI) 1.15-2.18, p=0.01). This was principally explained by a longer time to surgery (5.2 days ± 3.2 vs 2.7 ± 2.3 and 2.7 ± 2.2, p0.001). The three hospitals also differed in the rate of subjects losing the ability in ADLs after 6 months from the fracture (54.2%, 61%, 43.5%, p=0.016), while no statistical differences were found in the recovery of independent ambulation. On the basis of multivariate models, a lower access to post-acute rehabilitation could account for lower outcome in functional status.This study suggests that system factors such as time to surgery and rehabilitation resources can affect functional recovery and 1-year mortality in orthogeriatric units and they could explain different outcomes when comparing care models.

Hip fractures represent a major challenge for physicians as well as society as a whole. Both poor functional status and delay to surgery are well known risk factors for negative outcomes. We hypothesized that the timing of the operation is more important for frail older people than older people without functional limitations before fracture.We performed a prospective multicenter cohort study on 806 consecutive patients, 75 years of age or older, admitted with a fragility hip fracture to three hospitals in the Emilia-Romagna Region (Italy). All three hospitals had a comanaged care model, and the patients were under the shared responsibility of an orthopedic surgeon and a geriatrician.Functional status assessed as instrumental activities of daily living was an important predictor of survival after 1 year from fracture. After adjusting for confounders, the hazard ratios per 1 point score of increase from 0 to 8 was 1.30 (95% confidence interval 1.19-1.42, p = .000). Time to surgery increased 1-year mortality in patients with a low instrumental activities of daily living score (hazard ratios per day of surgical delay 1.14, 95% confidence interval 1.06-1.22, p.001) and intermediate instrumental activities of daily living score (hazard ratios 1.21, 95% confidence interval 1.09-1.34, p.001) but was an insignificant risk factor in functionally independent patients (hazard ratios 1.05 95% confidence interval 0.79-1.41, p = .706).Surgery delay is an independent factor for mortality in older patients after hip fracture but only for the frail older people with prefracture functional impairment. If our results are confirmed, a more intensive approach should be adopted for older people with hip fractures who have disabilities.

BACKGROUND The role of bisphosphonates (BPs) in the management of patients with hypercalciuria (HC) associated with osteoporosis is still uncertain. The aim of the study was to evaluate the effect of alendronate and indapamide alone or in combination on bone mineral density (BMD) and 24-h urinary calcium excretion (24-CaU) in post-menopausal women with HC and low BMD. METHODS A total of 77 post-menopausal women with HC (24-CaU > 4 mg/kg/day) and low BMD [T-score < -2.0 at lumbar spine (LS), femoral neck (FN) or total hip (TH)] from two centres of Northern Italy were randomized to receive indapamide 2.5 mg daily alone (24 patients, IND group), alendronate 70 mg weekly alone (27 patients, ALN group) or the combination therapy (26 patients, ALN + IND group). Throughout the study, all subjects received daily calcium supplements, depending on their dietary intake, to maintain a daily input of 1000 mg. Patients were instructed to increase water intake up to 2000 mL daily. The percentage and absolute changes of BMD at LS, FN and TH, and the variation of 24-CaU from baseline at 1 year were the primary outcomes. Serum calcium, phosphate, parathyroid hormone and bone alkaline phosphatase were also measured. RESULTS Overall 67 women completed the study and were included in the final analysis. Patients in the three groups were similar with regard to baseline characteristics. BMD did not significantly change from baseline after 1 year of treatment with indapamide (LS: +1 +/- 3.1%; FN: -0.3 +/- 3.5%; TH: -0.4 +/- 3.1%), while it showed a significant increase from baseline in the other two groups (ALN; LS: +5.8 +/- 4.2%, P < 0.001; FN: +3.9 +/- 7.9%, P = 0.018; TH: +2 +/- 3.6%, P = 0.006) (ALN + IND; LS: +8.2 +/- 5.3%, P < 0.001; FN: +4.9 +/- 6.7%, P = 0.007; TH: +2.9 +/- 4.2%, P = 0.004). Patients in the combination group showed a significantly higher increase of BMD at LS compared to ALN (P = 0.04). After 1 year, 24-CaU values significantly decreased from baseline in all groups (IND, 239 +/- 78 versus 364 +/- 44, P < 0.001) (ALN, 279 +/- 68 versus 379 +/- 79, P < 0.001) (ALN + IND, 191 +/- 68 versus 390 +/- 55, P < 0.001). The mean percentage decrease of 24-CaU in ALN + IND group (-50%) was significantly greater compared to ALN (-24%, P < 0.001) and IND (-35%, P = 0.012). CONCLUSIONS These results show a benefit, in terms of BMD improvement and 24-CaU reduction, associated with BPs' therapy in combination with indapamide in HC associated with osteoporosis. The combination therapy demonstrated a reduction of 24-CaU and an increase in LS BMD superior to that observed with alendronate alone. Our results support a new potential approach with BPs associated with thiazide diuretics or indapamide in the management of post-menopausal women with HC and associated bone loss. Studies on the larger sample size are needed to demonstrate the efficacy on the fracture outcome.

All hip fracture (HF) subjects are candidates for calcium and vitamin D (CaD) supplementation. Up to 50% of HF older adults present with secondary hyperparathyroidism (HPTH) resulting from hypovitaminosis D on hospital admission. To investigate the patterns and predictors of persistence with CaD supplementation in the elderly after HF, we considered all patients aged 70 years or older who were discharged alive after surgical repair of HF in the period of 1 year from an Orthopaedic Unit. Baseline characteristics of the subjects and osteoporosis treatment prescribed at discharge were retrieved from medical record review. A telephone interview at 6 months evaluated whether patients were currently taking CaD supplementation. Nonpersistence was defined when subjects ceased therapy within 6 months. Univariate and multivariate models were applied to determine the relationship between 6 months persistence with CaD and the variables collected: age, living situation, prescription of a bisphosphonate, baseline walking ability, number of drugs used, presence of dementia, number of active clinical issues at discharge (ACIs), discharge location, and being referred to a center for metabolic bone diseases (preplanned visit) at discharge. Of 428 subjects enrolled, 117 were excluded for different reasons (incomplete data, no therapy, death). A total of 311 subjects were discharged with a prescription of CaD (calcium 1,000 mg, cholecalciferol 800 UI, once daily) and were considered for the analysis. At 6 months, only 114 patients (36.7%) were currently taking CaD supplementation. In a univariate analysis, the following variables were significantly related with persistence: absence of dementia, prescription of a bisphosphonate, six or fewer drugs being used (drugs usedor=6), two or less ACIs (or=2 ACIs) at discharge, ability to walk without aid at baseline, being discharged home, and being referred to a preplanned visit. In a multivariate model, the prescription of a bisphosphonate at discharge (OR 3.178, 95% CI 1.477-6.836, P = 0.003), a preplanned visit (OR 1.953, 95% CI 1.066-3.514, P = 0.03), the absence of dementia (OR 1.877, 95% CI 1.021-3.451, P = 0.043), andor=6 drugs used (OR 1.842, 95% CI 1.066-3.182, P = 0.029) remained the most significant predictors of persistence with CaD. In HF elderly, who are at high risk of hypovitaminosis D and HPTH, persistence with CaD supplementation is very low. The enrolment in a postsurgical program for the management of bone disease can significantly increase persistence. Moreover, factors related to the complexity of older adult patients (polypharmacotherapy, dementia) seem to be particularly important in compliance with prescribed drugs.

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. 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. 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. 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. 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.

Giusti A, Barone A, Oliveri M, Pizzonia M, Razzano M, Palummeri E, Pioli G. An analysis of the feasibility of home rehabilitation among elderly people with proximal femoral fractures. Objective To evaluate the feasibility and predictors of success of home-based rehabilitation (HBR) in older adults after hip fracture. Design Prospective inception cohort study with 12 months of follow-up. Setting Acute and subacute care with follow-up in a community setting in Italy. Participants Community-dwelling older adults (N=199) aged 70 years or older, discharged from an acute orthopedic unit after repair of a nontraumatic proximal femoral fracture. Interventions Patients' choice of pursuing HBR or institutional-based rehabilitation (IBR). Main Outcome Measures Proportion of subjects discharged home for rehabilitation. Rates of institutionalization assessed at 3, 6, and 12 months postdischarge. Mean changes of the Barthel Index from baseline and proportion of subjects who regained their prefracture levels of function at the time of follow-up in the 2 intervention groups (HBR, IBR). Results Ninety-nine (49.7%) patients chose HBR, and the rest (50.3%) were discharged to a rehabilitation facility. With regard to the baseline characteristics, the 2 patient groups (HBR, IBR) differed with respect to living arrangement ( P ≤.001), prefracture functional status in basic (Barthel Index, P =.033; Katz Index, P =.041) and instrumental activities of daily living (IADLs) ( P =.041), and occurrence of delirium ( P =.022). During the follow-up, the number of subjects institutionalized at 3, 6, and 12 months was 52, 26, and 22, respectively. In the multiple logistic regression model, the only significant variable affecting the choice of IBR at discharge was the absence of relatives at home (odds ratio [OR], 6.7; 95% confidence interval [CI], 3.33–13.46; P ≤.001), whereas a prefracture functional impairment in more than 3 IADLs (at 12mo: OR=3.99; 95% CI, 1.57–10.18; P =.004), the absence of relatives at home (at 12mo: OR=8.81; 95% CI, 2.47–31.46; P =.001), and delay to surgery longer than 3 days (at 12 mo: OR=5.51; 95% CI, 1.28–23.81; P =.022) resulted in significant risk factors for long-term institutionalization. Compared with subjects who received traditional rehabilitation, those discharged home showed—after controlling for prefracture Barthel Index score, IADLs, cognitive status and age—a slightly lower functional decline and a higher rate of recovery during the follow-up (mean change in Barthel Index score ± standard deviation at 12mo: HBR, −11.2±24.7 vs IBR, −23.7±28.5; P =.015). Conclusions In an unselected population of hip-fractured older adults previously living in the community, HBR seems to be a feasible alternative to IBR in those subjects living with relatives.

This document is a Joint Position Statement by Gruppo Italiano di OrtoGeriatria (GIOG) supported by Societa Italiana di Gerontologia e Geriatria (SIGG), and Associazione Italiana Psicogeriatria (AIP) on management of hip fracture older patients. Orthogeriatric care is at present the best model of care to improve results in older patients after hip fracture. The implementation of orthogeriatric model of care, based on the collaboration between orthopaedic surgeons and geriatricians, must take into account the local availability of resources and facilities and should be integrated into the local context. At the same time the programme must be based on the best available evidences and planned following accepted quality standards that ensure the efficacy of the intervention. The position paper focused on eight quality standards for the management of hip fracture older patients in orthogeriatric model of care. The GIOG promotes the development of a clinic database with the aim of obtaining a qualitative improvement in the management of hip fracture.

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.

To compare the effects on parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25(OH)D) of two dosing regimens of cholecalciferol in women with secondary hyperparathyroidism (sHPTH) and hypovitaminosis D and to investigate variables affecting 25(OH)D response to cholecalciferol.Randomized-controlled trial with 6-month follow-up.Two osteoporosis centers in northern Italy.Sixty community-dwelling women aged 65 and older with sHPTH and hypovitaminosis D, creatinine clearance greater than 65 mL/min and without diseases or drugs known to influence bone and vitamin D metabolism.Cholecalciferol 300,000 IU every 3 months, once at baseline and once at 3 months (intermittent D(3) group) or cholecalciferol 1,000 IU/day (daily D(3) group).Serum PTH, 25(OH)D, calcium, bone-specific alkaline phosphatase, β-C-terminal telopeptide of type I collagen, phosphate, 24-hour urinary calcium excretion.The two groups had similar baseline characteristics. All participants had vitamin D deficiency [25(OH)D20 ng/mL)], and 36 subjects (60%) had severe deficiency (10 ng/mL), with no difference between the groups (severe deficiency: intermittent D(3) group, n=18; daily D(3) group, n=18). After 3 and 6 months, both groups had a significant increase in 25(OH)D and a reduction in PTH. Mean absolute increase ± standard deviation of 25(OH)D at 6 months was higher in the intermittent D(3) group (22.7±11.8 ng/mL) than in the daily D(3) group (13.7±6.7 ng/mL, P.001), with a higher proportion of participants in the intermittent D(3) group reaching desirable serum concentration of 25(OH)D≥30 ng/mL (55% in the intermittent D(3) group vs 20% in the daily D(3) group, P.001). Mean percentage decrease of PTH in the two groups was comparable, and at 6 months, a similar proportion of participants reached normal PTH values. 25(OH)D response to cholecalciferol showed a wide variability. In a logistic regression analysis, body mass index and type of treatment appeared to be significantly associated with normalization of 25(OH)D values.Cholecalciferol 300,000 IU every 3 months was more effective than 1,000 IU daily in correcting vitamin D deficiency, although the two groups achieved similar effects on PTH at 6 months. Only 55% of the higher-dose intermittent group reached desirable concentrations of 25(OH)D, suggesting that yet-higher doses will be required for adequate vitamin D repletion.

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.

Barone A, Giusti A, Pizzonia M, Razzano M, Oliveri M, Palummeri E, Pioli G. Factors associated with an immediate weight-bearing and early ambulation program for older adults after hip fracture repair. Objective To evaluate baseline characteristics and in-hospital factors associated with nonadherence with an immediate weight-bearing and early ambulation (IWB-EA) program after hip fracture (HF) surgery. Design Prospective inception cohort study. Setting Ortho-geriatric unit in an acute care hospital. Participants Older adults (N=469) admitted with an osteoporotic HF who underwent surgery. Interventions Immediate weight-bearing and assisted ambulation training on the first postoperative day (all patients). Main Outcome Measure Proportion of subjects who adhered to the IWB-EA protocol within 48 hours of surgery. Results A total of 366 patients (78%) bore weight and ambulated within 48 hours (weight-bearing [WB] group) while the others did not adhere to the protocol (nonweight-bearing [NWB] group). Subjects in the NWB group were significantly older, were more cognitively and functionally impaired, and presented a higher comorbidity at baseline. A higher proportion of subjects in the NWB group (42.7%) than the WB group (23.5%; P Conclusions This study establishes that IWB-EA is feasible in a high proportion of patients after surgical stabilization of HF. Neither cognitive impairment nor high comorbidity influenced significantly the adherence to the protocol, indicating that IWB-EA may be offered to an unselected population of the elderly with HF. The day of surgery (eg, preholiday or not) was the only variable influencing the participation to the IWB-EA protocol, suggesting the importance of maintaining the same standard of daytime care every day of the week.

Background and aims: Few studies have investigated predictors for hospital readmission after hip fracture repair. Methods: In a prospective cohort study we evaluated factors associated with early (within 3 months) and late (between 3–12 months), single and multiple hospital readmission in 236 hip-fractured older adults admitted to an orthopedic unit. Baseline patient characteristics and hospital course (functional and cognitive status, comorbidity, type of fracture, time to surgery, in-hospital stay, complications) were recorded. Hospital readmission over 12 months and ICD-9 principal diagnosis were ascertained from administrative sources. Functional status at the end of the rehabilitation program was assessed by telephone interviews. Results: Seventy-one patients (30.1%) were readmitted to hospital within twelve months of discharge and 22 (9.3%) had two or more readmission. The total number of readmissions was 105, 43 (41%) occurred in the first three months. The most common readmission causes were cardiac, infectious and cerebrovascular; surgical complication accounted for 5.7%. Patients with a single readmission, like those with multiple readmissions, were sicker (CIRS-CIsubscore 4.0±1.8 vs 3.2±1.6, p=0.010) and more functionally impaired at the end of rehabilitation (2 months’ Katz index 2.1±2 vs 2.9±2.3, p=0.007) than controls. In a multiple logistic regression model, comorbidity and functional status at the end of rehabilitation were the only factors associated with the risk of readmission. Conclusions: Subjects at high risk of readmission can be reliably assessed, since few significant variables were associated with rehospitalization. Subgroups of patients with an elevated risk of rehospitalization after hip fracture may be the target for strategies to reduce the burden of excessive hospital use and improve overall outcomes.

Hip fracture (HF) is a major health care problem in the Western world, associated with significant morbidity, mortality and loss of function. Its incidence is expected to increase as the population ages. The authors discuss the role of a coordinated multidisciplinary team in the management of patients during hospital stay, at discharge and during rehabilitation. Orthogeriatric care should not just be viewed as a multidisciplinary activity, but as a radical alternative to the traditional model of care, an alternative based on all those strategies in which evidence shows an improvement in outcomes in the fractured elderly. Therefore, key points of the care are early surgery, immediate mobilization, prevention and management of delirium, pain and malnutrition, as well as an integrated and multidisciplinary approach. Comprehensive geriatric assessment is useful in identifying frail elderly and in providing information that is essential in formulating clinical recommendations and making care plans. In each hospital, the orthogeriatric unit should represent a center of excellence for treating elderly patients with major fractures. However, when an orthogeriatric project is implemented, it is essential that detailed data about the case-mix of patients, process of care and outcomes are collected, to compare the results with historical data and to be able to participate in audit processes.

The aim of the study was to investigate the metabolic clearance rate (MCR) and the secretion rate (SR) of calcitonin (CT) in elderly men and women (mean age +/- SE: 75 +/- 3 and 78 +/- 3 yr, respectively). The basal levels of CT were higher in men than in women (9.6 +/- 3.2 vs 6.0 +/- 1.5 pg/ml; p less than 0.05). The MCR was not significantly different between sexes (905 +/- 54.2 vs 810 +/- 165.1 l/day). In contrast, CT SR was significantly higher in male subjects compared to women (8.7 +/- 3.1 vs 4.8 +/- 1.5 micrograms/day; p less than 0.05). These findings suggest that only a few units of CT are secreted daily by elderly subjects and that the lower basal values of the hormone in women are probably the result of a lower production rate.

The aim of this study was to evaluate beta-endorphin, ACTH, and cortisol plasma levels during metyrapone administration in man after chronic opioid receptor stimulation. Metyrapone (750 mg every 4 hr for 6 doses) was administered to ten male heroin addicts, who had been on a maintenance therapy with methadone for at least 6 months and to ten healthy sex- and age-matched volunteers. Before metyrapone administration the basal levels of cortisol and ACTH were significantly decreased in addicts as compared to normal controls, while plasma beta-endorphin was not different. The response of beta-endorphin and ACTH to metyrapone administration was significantly blunted in addicts (p less than 0.01). These results suggest that the chronic stimulation of opiate receptors can impair the function of the anterior pituitary gland.

It has been suggested that the analgesic action of calcitonin (CT) might involve a stimulation of beta-endorphin (beta-EP) release. To verify whether salmon CT modifies the circulating levels of beta-EP, and whether the route of administration plays any role in this response, we have studied 10 healthy male volunteers, aged 30-40 yr. Each of them was studied on 4 different days, after administration of placebo or salmon CT (100 UI) by the intravenous, intramuscular and nasal route, in random order. Ionized calcium tended to decrease, especially after intravenous CT, but there was no change in plasma beta-EP levels, regardless of the route of administration. It is therefore unlikely that circulating beta-EP mediates any biological effect of CT.

To determine whether secondary hyperparathyroidism (HPTH) due to hypovitaminosis D affects bone mineral density (BMD) response to alendronate (ALN) in elderly women with osteoporosis.Randomized, controlled trial with 1-year follow-up.Two osteoporosis centers in northern Italy.Community-dwelling women aged 60 and older with a BMD T-score below -2.5 and secondary HPTH with vitamin D insufficiency.One hundred twenty subjects were randomly assigned to receive ALN 70 mg once a week alone or ALN 70 mg once a week plus calcitriol (1,25D3) 0.5 microg daily.BMD measured using dual-energy x-ray absorptiometry at the lumbar spine (L1-L4), femoral neck, and total hip and serum levels of intact PTH at baseline and 12 months.After 1 year, BMD of the lumbar spine, femoral neck, and total hip significantly increased from baseline in both groups (P.001). Patients allocated to ALN plus 1,25D3 demonstrated a significantly higher increase in lumbar spine BMD than those receiving ALN alone (mean percentage+/-standard deviation 6.8+/-4.6 vs 3.7+/-3.2, P.001). Serum levels of PTH did not change significantly at 1 year in the ALN group (mean percentage, -3.7+/-27.1, P=.13) but decreased significantly in the ALN plus 1,25D3 group (-32.1+/-22.1, P.001). At 12 months, subjects with normalized PTH independent of therapy allocation had a greater increase in lumbar spine BMD than those with persistent HPTH (6.5+/-4.6% vs 3.7+/-3.4%, P.001). Lumbar spine BMD changes showed a significant negative correlation with PTH at 1 year (correlation coefficient (rho) =-0.399, P.001) and a positive correlation with PTH changes (i.e., baseline value - 1 year value; rho=0.295, P=.005).Persistence of secondary HPTH reduces BMD response to ALN in older women with osteoporosis.

Background and aims: The study investigates one-year mortality risk associated with hip fracture in elderly people, and pre-fracture characteristics and events occurring during the acute phase which may represent significant predictors for acute and long-term mortality. Methods: The study is a prospective cohort study of 252 patients aged 70 and older, consecutively admitted with hip fracture to the Division of Orthopedic Surgery of the Galliera Hospital of Genoa, Italy. At admission, each subject received a standardized diagnostic evaluation, including demographic variables, biochemical markers of nutritional status and basic medical, functional and cognitive assessment. Patients were followed by telephone interviews at three months, six months and one year after fracture. The relationship between mortality and the risk factors recorded was assessed using logistic regression models. Results: 248 patients were eligible. Cumulative mortality was 4.8% during hospital stay, and 12.5% at 3, 18.9% at 6 and 24% at 12 months. The risk factors significantly associated with mortality were: sex, Acute Physiology Score (APS), comorbidity, functional and cognitive status, and albumin levels. In multivariate models, albumin below 3 g/dL remained the only significant predictor of in-hospital mortality (OR 6,8, 95% CI 1.56-29,7, p

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.

In older people, hip fractures often lead to disability and death. We evaluated handgrip strength, an objective measure of physical function for bedridden patients, as a predictor of walking recovery in the year after fracture surgery.This multicenter prospective cohort study included 504 patients, aged 70 years or more, who were admitted to the hospital for hip fracture surgery and were formerly able to walk independently. A multidimensional geriatric evaluation that included a physical examination, Short Portable Mental Status Questionnaire, Geriatric Depression Scale, Charlson Index, Basic Activities of Daily Living, and grip strength was administered at the time of admission. Follow-ups were performed every 3 months for 1 year after surgery to assess functional status and survival. The walking recovery probability was evaluated using multivariable logistic regression models.The mean age of the participants was 85.3 ± 5.5 years, and 76.1% of the participants were women. The mean grip strength was greater in men (β: 6.6 ± 0.62, P.001) and was directly related to the Short Portable Mental Status Questionnaire results (P.001), Basic Activities of Daily Living results (P.001), serum vitamin D levels (P = .03), and time before surgery (P.001), whereas it was inversely related to age (P.001), Geriatric Depression Scale score (P.001), and Charlson Index (P.001). After adjusting for confounders, the grip strength was directly associated with the probability of both incident and persistent walking recovery (odds ratio highest tertile vs lowest tertile, 2.84, confidence interval, 1.76-4.59 and 2.79, confidence interval, 1.35-5.79, respectively).In older patients with hip fractures, early grip strength evaluation might provide important prognostic information regarding the patient's future functional trajectory.

The response of PRL, FSH and LH to saunainduced 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

In the present study we have examined the response of endogenous opiates (beta-EP and Met-enk) and ACTH to a particular type of thermal stimulus such as sauna in 8 young healthy subjects. Sauna-induced hyperthermia resulted in an increase of plasma beta-EP and ACTH, but appeared to have no significant effect on circulating Met-enk. The different responses of ACTH, beta-EP and Met-enk to heat exposure indicate that hyperthermia represents a form of stress, which can trigger off a well-defined neuroendocrine reaction.

To study the short-term effects on mineral and bone metabolism of a recently introduced amino-diphosphonate (4-amino-1-hydroxybutylidene-1,1-diphosphonate or ABDP), 10 patients suffering from active Paget's disease were examined. Each subject received intravenously 5 mg/day of ABDP for 4 days and the effects of treatment were monitored for 12 days. ABDP administration was followed by an early and significant decrease of the urinary hydroxyproline and calcium excretion, of the theoretical renal threshold for phosphate of the serum calcium. Serum phosphate also decreased, while its urinary excretion increased. Intact parathyroid hormone levels at the end of treatment were four times higher than basal levels. Total and bone alkaline phosphatase tended to decrease only slightly at the end of the observation, whereas serum osteocalcin, tended to increase. These findings indicate that the earlier effect of ABDP is a profound inhibition of bone resorption, which brings about a compensatory parathyroid hormone response. The decrease of urinary hydroxyproline follows an exponential curve, with a calculated half-life of 2.2 days, suggesting an approximate equivalency of 5 mg/day ABDP to slightly more than 30 mg/day 3-amino-1-hydroxypropylidene-1,1-diphosphonate. Bone formation seems scarcely influenced in the short-term, but osteoblastic indices show a contrasting behaviour, which may reflect a different biological origin and/or significance.

In order to study the effects of a physiologic meal on calcitonin (CT) secretion we studied 6 normal male volunteers (aged 28-34 yr). Each subject was given, on two separate days, either a mixed meal or 200 ml of distilled water, in random order. Gastrin (G) was effectively stimulated by the meal (F = 8.82; p less than 0.001) and reached a peak (with an average 100% increase) 30 min after the end of the meal, slowly decreasing thereafter; no increase was seen after water ingestion. On the other hand, CT levels remained stable throughout the observation period on both occasions. Ionized and total calcium did not show significant variations either after the meal or after water ingestion. These findings suggest that G alone, at the concentrations usually reached after a physiologic meal, is unable to stimulate CT secretion, at least in the absence of calcium increases.

Because a series of reports suggests the existence of altered bone and mineral metabolism in diabetes mellitus, we studied 106 diabetic subjects (42 insulin-dependent (IDD) and 64 noninsulin dependent (NIDD] to determine whether a difference in bone turnover (evaluated by serum osteocalcin (OC] could be found in comparison with normal controls. OC levels in diabetic subjects were lower than the age- and sex-specific predicted values. The reduction was especially evident in male and female NIDD (Z-score: - 1.12 +/- 0.92, t = 8.4, P less than 0.001 and -0.84 +/- 0.86, t = 4.0, P less than 0.01, respectively) and male IDD (Z-score: - 0.90 +/- 0.86, t = 4.5, P less than 0.01). The mean Z-score for female IDD, albeit negative (-0.31 +/- 0.79; t = 1.6; 0.2 greater than P greater than 0.1), was not significantly different from normal. Total serum calcium (Ca) and calcitonin (CT) showed an opposite pattern, being higher in all the diabetic subgroups (with the exception of Ca in female IDD), whereas parathyroid hormone (PTH) was lower than expected in each diabetic subset. By multiple regression analysis, the reduction of OC was related to PTH and CT levels and to the type of treatment. Subjects controlled with diet showed differences of greater magnitude from the expected normal values than those treated with oral hypoglycemic agents or insulin (Z-score: -1.28 +/- 1.05 vs. -0.85 +/- 0.90 and -0.63 +/- 0.97, respectively; P = 0.05). However, the variance explained by these three factors was small, suggesting that other variables (possibly 1 alpha,25(OH)2D) exerted important influences on OC levels.

The Authors examined interleukin 1 (IL-1) secretion from the peripheral and medullary mononuclear cells, obtained with sequential separation on Ficoll-Hypaque and 45% Percoll gradient, in 6 pagetic subjects and 6 normal controls. Both peripheral and medullary cells from pagetic subjects showed a significantly greater IL-1 production after stimulation with lipopolysaccharides (LPS); moreover, we observed a spontaneous IL-1 release from medullary cells in pagetic subjects but not in normal controls. These findings suggest a possible role of IL-1 in the elevated bone turnover of Paget's disease of bone.

To evaluate the responses of circulating β-endorphin, met-enkephalin and ACTH to sauna-induced hyperthermia, 8 male heroin addicts recently admitted to a therapeutic community and 8 age-matched normal subjects were examined. Compared with control subjects, heroin addicts showed 1. A decrease of the basal levels of β-endorphin; 2. Absence of the normal increase of β-endorphin and ACTH after sauna; 3. A lower increase in systolic blood pressure. It is concluded that an impairment of the adaptive response to stress may be present in heroin addicts, even after a relatively short drug-free period (14 days).

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

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.

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.

In order to establish the normal range of serum Calcitonin (CT), evaluated with a new, sensitive radioimmunoassay in normal women of various ages, 67 female subjects were examined. CT levels were detectable in all the subjects, with a reference interval (bounded by the 2.5 and 97.5 percentiles) of 3.6-16.9 pg/ml; a very slight decrease with age was observed (correlation coefficient = -0.24; P = 0.05; regression equation: CT = 9.55--0.042 x age). This assay seems sensitive enough to permit the measurement of CT in physiological conditions.