Leonardo Sartori

Effects of Oral Alendronate in Elderly Patients with Osteoporosis and Mild Primary Hyperparathyroidism

In a large proportion of the patients with primary hyperparathyroidism (PHPT), a variable degree of osteopenia is the only relevant manifestation of the disease. Low bone mineral density (BMD) in patients with PHPT is an indication for surgical intervention because successful parathyroidectomy results in a dramatic increase in BMD. However, low BMD values are almost an invariable finding in elderly women with PHPT, who are often either unwilling or considered unfit for surgery. Bisphosphonates are capable of suppressing parathyroid hormone (PTH)‐mediated bone resorption and are useful for the prevention and treatment of postmenopausal osteoporosis. In this pilot‐controlled study, we investigated the effects of oral treatment with alendronate on BMD and biochemical markers of calcium and bone metabolism in elderly women presenting osteoporosis and mild PHPT. Twenty‐six elderly patients aged 67–81 years were randomized for treatment with either oral 10 mg alendronate on alternate‐day treatment or no treatment for 2 years. In the control untreated patients a slight significant decrease was observed for total body and femoral neck BMD, without significant changes in biochemical markers of calcium and bone metabolism during the 2 years of observation. Urine deoxypyridinoline (Dpyr) excretion significantly fell within the first month of treatment with alendronate, while serum markers of bone formation alkaline phosphatase and osteocalcin fell more gradually and the decrease became significant only after 3 months of treatment; thereafter all bone turnover markers remained consistently suppressed during alendronate treatment. After 2 years in this group we observed statistically significant increases in BMD at lumbar spine, total hip, and total body (+8.6 ± 3.0%, +4.8 ± 3.9%, and +1.2 ± 1.4% changes vs. baseline mean ± SD) versus both baseline and control patients. Serum calcium, serum phosphate, and urinary calcium excretion significantly decreased during the first 3‐6 months but rose back to the baseline values afterward. Increase in serum PTH level was statistically significant during the first year of treatment. These preliminary results may make alendronate a candidate as a supportive therapy in patients with mild PHPT who are unwilling or are unsuitable for surgery, and for whom osteoporosis is a reason of concern.

Alendronate Prevents Further Bone Loss in Renal Transplant Recipients

The aim of this study was to investigate the effects of alendronate, calcitriol, and calcium in bone loss after kidney transplantation. We enrolled 40 patients (27 men and 13 women, aged 44.2 ± 11.6 years) who had received renal allograft at least 6 months before (time since transplant, 61.2 ± 44.6 months). At baseline, parathyroid hormone (PTH) was elevated in 53% of the patients and the Z scores for bone alkaline phosphatase (b‐ALP) and urinary type I collagen cross‐linked N‐telopeptide (u‐NTX) were higher than expected (p < 0.001). T scores for the lumbar spine (−2.4 ± 1.0), total femur (−2.0 ± 0.7), and femoral neck (−2.2 ± 0.6) were reduced (p < 0.001). After the first observation, patients were advised to adhere to a diet containing 980 mg of calcium daily and their clinical, biochemical, and densitometric parameters were reassessed 1 year later. During this period, bone density decreased at the spine (−2.6 ± 5.7%; p < 0.01), total femur (−1.4 ± 4.2%; p < 0.05), and femoral neck (−2.0 ± 3.0%; p < 0.001). Then, the patients were randomized into two groups: (1) group A—10 mg/day of alendronate, 0.50 μg/day of calcitriol, and 500 mg/day of calcium carbonate; and (2) group B—0.50 μg/day of calcitriol and 500 mg/day of calcium carbonate. A further metabolic and densitometric reevaluation was performed after the 12‐month treatment period. At the randomization time, group A and group B patients did not differ as to the main demographic and clinical variables. After treatment, bone turnover markers showed a nonsignificant fall in group B patients, while both b‐ALP and u‐NTX decreased significantly in alendronate‐treated patients. Bone density of the spine (+5.0 ± 4.4%), femoral neck (+4.5 ± 4.9%), and total femur (+3.9 ± 2.8%) increased significantly only in the alendronate‐treated patients. However, no trend toward further bone loss was noticed in calcitriol and calcium only treated subjects. No drug‐related major adverse effect was recorded in the two groups. We conclude that renal transplanted patients continue to loose bone even in the long‐term after the graft. Alendronate normalizes bone turnover and increases bone density. The association of calcitriol to this therapy seems to be advantageous for better controlling the complex abnormalities of skeletal metabolism encountered in these subjects.

Tooth loss in the elderly and its association with nutritional status, socio-economic and lifestyle factors

Objective. Tooth loss impacts on general health and is a risk factor for malnutrition, disability, loss of self-sufficiency, and deterioration in quality of life. The present study was carried out to evaluate the prevalence of edentulism and its association with social and lifestyle factors in a population of elderly Italians. Material and Methods. Dental, social, and disease conditions were evaluated in a large community-based cohort (3054) of elderly subjects (≥65 years) of both sexes in northern Italy. Logistic regression analyses with stepwise forward selection were performed to estimate the independent contribution of nutritional, socio-economic, and lifestyle variables to dental status. Adjusted ORs and 95% CI were estimated for variables significantly associated with edentulism. Results. The prevalence of edentulism was about 44.0%. It was more pronounced in females and it was twice as prevalent in the 90+ years age group. Among edentulous subjects, 17.5% wore no prostheses. Difficulties in chewing and in swallowing were reported by 47.6% and 13.7% of the subjects, respectively. Multivariate analysis indicates that edentulism was associated with age in both sexes. For women, independently associated risk factors were: years since menopause >23 (OR = 1.81; 95% CI: 1.37–2.40), number of children >3 (OR = 1.95; 95% CI: 1.36–2.80), and living alone (OR = 1.47; 95% CI: 1.15–1.88). For men, these were serum albumin <40 g/l (OR = 1.79; 95% CI: 1.22–2.63), current smoking (OR = 4.01; 95% CI: 2.59–6.20), and former smoking (OR = 3.42; 95% CI: 2.42–4.82). Conclusions. The prevalence of edentulism among the elderly Italian population studied was at the high end among Western countries, and higher in women than in men. In women, tooth loss correlated with aging, female events (pregnancies, menopausal status), and living alone. In men, aging and smoking are important determinants of edentulism, which is associated with the risk condition of hypoalbuminemia. Difficulty in chewing was associated with dentition type. In our study, the high prevalence of edentulous subjects without prostheses suggests a need for educational and social measures to improve patients’ attitudes to dental care and to encourage the use of prostheses among the elderly.

Self-report of difficulty in performing functional activities identifies a broad range of disability in old age.

OBJECTIVE: To describe a broad range of physical disability by examining the association between a four‐level measure of disability, based on self‐report of difficulty in performing functional activities, and previously identified risk factors for disability.

The effect of cardiovascular and osteoarticular diseases on disability in older Italian men and women: Rationale, design, and sample characteristics of the Progetto Veneto Anziani (PRO.V.A.) study

OBJECTIVES: Describe the methodology and preliminary results of the Progetto Veneto Anziani (PRO.V.A.) Study, an observational study of the Italian population aged 65 and older

Metabolic syndrome and all-cause and cardiovascular mortality in an Italian elderly population: the Progetto Veneto Anziani (Pro.V.A.) Study.

OBJECTIVE—The purpose of this study was to explore the association of metabolic syndrome and each of its components with all-cause and cardiovascular mortality in a general Italian elderly population. RESEARCH DESIGN AND METHODS—Metabolic syndrome, diagnosed by National Cholesterol Education Program Adult Treatment Panel III criteria, all-cause mortality, and cardiovascular mortality, was evaluated in 2,910 subjects aged ≥65 years of the Progetto Veneto Anziani (Pro.V.A.) Study during a mean follow-up time of 4.4 years. RESULTS—After multivariable adjustment, metabolic syndrome was associated with increased all-cause mortality in all subjects (hazard ratio 1.41 [95% CI 1.16–1.72], P = 0.001), among men (1.42 [1.06–1.89], P = 0.017), and among women (1.47 [1.13–1.91], P = 0.004). High glucose in all subjects (1.27 [1.02–1.59], P = 0.037) and in women (1.61 [1.16–2.24], P = 0.005) and low HDL cholesterol in women (1.48 [1.08–2.02], P = 0.014) were predictors of all-cause mortality, even independently of the interactions of different metabolic syndrome components. After multivariable adjustment, metabolic syndrome was also associated with increased cardiovascular mortality in all subjects (1.60 [1.17–2.19], P = 0.003), among men (1.66 [1.00–2.76], P = 0.051), and among women (1.60 [1.06–2.33], P = 0.025). High glucose (2.17 [1.28–3.68], P = 0.004) and low HDL cholesterol (1.78 [1.07–2.95], P = 0.026) among women predicted higher cardiovascular mortality. CONCLUSIONS—In this general Italian elderly population, among metabolic syndrome components, all-cause mortality is better predicted by high glucose in all subjects and in women and by low HDL cholesterol in women, whereas cardiovascular mortality is better predicted by high glucose and low HDL cholesterol in women.

Vitamin D and physical performance in elderly subjects: the Pro.V.A study.

Background The role of Vitamin D in musculoskeletal functionality among elderly people is still controversial. We investigated the association between serum 25-hydroxyvitamin D (25OHD) levels and physical performance in older adults. Methods 2694 community-dwelling elderly women and men from the Progetto Veneto Anziani (Pro.V.A.) were included. Physical performances were assessed by: tandem test, 5 timed chair stands (TCS), gait speed, 6-minute walking (6 mW) distance, handgrip strength, and quadriceps strength. For each test, separate general linear models and loess plots were obtained in both genders, in relation to serum 25OHD concentrations, controlling for several potential confounders. Results Linear associations with 25OHD levels were observed for TCS, gait speed, 6 mW test and handgrip strength, but not for tandem test and quadriceps strength. After adjusting for potential confounders, linear associations with 25OHD levels were still evident for the 6 mW distance in both genders (p = .0002 in women; <.0001 in men), for TCS in women (p = .004) and for gait speed (p = .0006) and handgrip strength (p = .03) in men. In loess analyses, performance in TCS in women, in gait speed and handgrip strength in men and in 6 mW in both genders, improved with increasing levels of 25OHD, with most of the improvements occurring for 25OHD levels from 20 to 100 nmol/L. Conclusion lower 25OHD levels are associated with a worse coordination and weaker strength (TCS) in women, a slower walking time and a lower upper limb strength in men, and a weaker aerobic capacity (6 mW) in both genders. For optimal physical performances, 25OHD concentrations of 100 nmol/L appear to be more advantageous in elderly men and women, and Vitamin D supplementation should be encouraged to maintain their 25OHD levels as high as this threshold.

Bone Mineral Density and Testicular Failure: Evidence for a Role of Vitamin D 25-Hydroxylase in Human Testis

WORKING HYPOTHESIS Mutations in the CYP2R1 gene, highly expressed in the testis and encoding vitamin D 25-hydroxylase, result in a vitamin D deficiency and a defective calcium homeostasis leading to rickets. OBJECTIVE Our aim was to investigate CYP2R1 expression in pathological testis samples and relate this to vitamin D metabolism in testiculopathic patients. DESIGN, PATIENTS, SETTING: Testis samples for in vitro study and 98 young men were transversally evaluated at Padovas Center for Male Gamete Cryopreservation. METHODS CYP2R1 mRNA expression and protein production were evaluated by quantitative RT-PCR, Western blot analysis, and immunofluorescence. Hormonal and bone-marker levels, and bone densitometry by dual-energy x-ray absorptiometry, were determined in patients with Sertoli-cell-only syndrome and severe hypospermatogenesis. RESULTS We found a lower gene and protein expression of CYP2R1 in samples with hypospermatogenesis and Sertoli-cell-only syndrome (P < 0.05) and a colocalization with INSL-3, a Leydig cell marker, at immunofluorescence. In all testiculopathic patients 25-hydroxyvitamin D levels were significantly lower and PTH levels higher compared to controls (P < 0.05). Furthermore, testiculopathic patients showed osteopenia and osteoporosis despite normal testosterone levels compared with controls both with increased bone-marker levels and altered dual-energy x-ray absorptiometry in the femoral neck and lumbar spine (for all parameters, P < 0.05). CONCLUSIONS Our data show an association between testiculopathy and alteration of the bone status, despite unvaried androgen and estrogen levels and no other evident cause of vitamin D reduction. Further studies in larger cohorts are needed to confirm our results.

Association of CTR and COLIA1 Alleles with BMD Values in Peri- and Postmenopausal Women

Abstract. The variability of bone mass and bone strength is in part genetically determined. The pathophysiology of the disease is complex and its heritability is almost certainly polygenic. In a large group of women from north eastern Italy, homogeneous for calcium intake and other risk factors for osteoporosis, we investigated three different genetic polymorphic markers that have been associated with bone mineral density (BMD). The study includes 663 postmenopausal (aged 48–85 years) and 52 perimenopausal (aged 47–53 years) women. Lumbar spine and hip BMD were measured by dual energy X-ray absorptiometry (DXA). After DNA extraction, the restriction enzymes utilized were MscI for the SP1 site of the collagen type I regulatory region (COLIA1), AluI for the calcitonin receptor (CTR) gene, and BsmI for the Vitamin D receptor (VDR) gene. COLIA1 genotype was significantly associated with age-adjusted hip BMD, with the highest values in the SS group and the lowest in the ss group (p < 0.05). The COLIA1 effect was not visible until the sixth decade of life, but it increased thereafter with aging, becoming statistically significant also at the lumbar spine in subjects aged >70 years. CTR genotype was also significantly related to bone mass in the CC group, with the lowest age and weight-adjusted BMD values at the spine (p < 0.05). The CTR genotype effect was greater in the younger subset of women. This suggests that the CTR genotype might influence the process of acquiring peak bone mass rather than the process of bone loss along aging. No trend association was found between BMD values and VDR genotype. These findings suggest an association between the COLIA1 gene polymorphism more with the age-related rate of bone loss than with peak bone mass, which apparently is somewhat affected by CTR gene polymorphism.

The impact of knee and hip chondrocalcinosis on disability in older people: the ProVA Study from northeastern Italy

Objectives Chondrocalcinosis is frequently associated with osteoarthritis. The role of osteoarthritis in the onset and progression of disability is well known. The impact of chondrocalcinosis on disability has never been investigated in epidemiological studies. Methods Progetto Veneto Anziani is a survey of 3099 older Italians, focusing on chronic diseases and disability. Assessment was by questionnaires, physical performance tests and clinical evaluations. Chondrocalcinosis was determined by x-ray readings of 1629 consecutive subjects. Knee and hip osteoarthritis severity was evaluated by summing the radiographic features score (RFS) assigned during x-ray reading. Results Subjects with chondrocalcinosis were older and more frequently women (age-adjusted p<0.0001). The gender association disappeared following adjustment for osteoarthritis severity. However, at the knee, the prevalence of osteoarthritis was higher in chondrocalcinosis patients independently of age and sex (age-adjusted p<0.0001). No difference was found between chondrocalcinosis and controls in sociodemographic variables and comorbidity. Knee chondrocalcinosis was strongly associated with clinical features of knee osteoarthritis and with disability assessment parameters in the bivariate analysis. Most associations remained after adjusting for age. After further adjustment for RFS, a significant association remained for knee deformity and pain, the need for a cane, difficulty walking 500 m, using a toilet, shopping and repeatedly rising from a chair. Conclusions Pain and physical function are the outcome measures of choice for assessing disability in osteoarthritis patients. The presence of chondrocalcinosis contributes to both, independently of age and osteoarthritis severity, thus compromising the quality of life and worsening comorbidity.