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Biomedical subjects

R Rizzoli

Publications and source records attributed to R Rizzoli.

At least 55 records · Page 3Linked to original sources

Gain in bone mineral mass in prepubertal girls 3.5 years after discontinuation of calcium supplementation: a follow-up study.

BACKGROUND: Calcium supplementation during childhood and adolescence increases bone-mass accrual. Whether or not this benefit persists after discontinuation of supplementation is not known. We previously showed a favourable effect of milk-extracted calcium phosphate incorporated in various foods on accumulation of bone mineral mass in 8-year-old girls. We now report the results of a follow-up study undertaken more than 3 years after the end of calcium supplementation. METHODS: Anthropometric and bone variables were measured in 116 of the 144 girls whose data had been studied at the end of the supplementation period. The mean time elapsed between the end of the intervention period and this follow-up measurement was 3.5 years. Areal bone mineral density was measured by dual-energy X-ray absorptiometry at the same six skeletal sites as those studied during the intervention phase. FINDINGS: We were able to remeasure 62 and 54 girls of the calcium-supplemented and placebo groups, respectively. The increase from baseline in the overall mean bone mineral density of the six skeletal sites was still highly significant (calcium-supplemented group 179 mg/cm(2) [SE 8] vs placebo group 151 mg/cm(2) [7], p=0.012). A significant difference in favour of the supplemented group was also seen with respect to mean bone mineral content (p=0.031) and mean bone area (p=0.04). Difference in pubertal maturation did not seem to account for the recorded differences. INTERPRETATION: Our results suggest that this form of milk-extracted calcium phosphate taken during the prepubertal period can modify the trajectory of bone mass growth and cause a long-standing increase in bone mass accrual, which lasts beyond the end of supplementation.

Absorptiometry, Photon↗

Allogeneic bone marrow transplantation is associated with a preferential femoral neck bone loss.

Osteoporosis is a major complication of organ transplantation. Little is known about the risk of developing osteoporosis in bone marrow transplant (BMT) recipients. We studied early and late changes in bone mineral density (BMD), as well as biochemical markers of bone remodeling, in patients at the time of allogeneic BMT (alloBMT) and up to 13 years thereafter. In a cross-sectional study, 102 patients (40 women, 62 men, mean age +/- SEM, 38.9 +/- 1.6 years) were segregated into a first group (A, n = 48) and evaluated before or during the first weeks (mean +/- SD 0.3 +/- 0.1 month, range -0.5 to 3 months) following alloBMT, and a second group (B, n = 54) studied 60.1 +/- 5.6 months (range 6-156 months) following alloBMT. Lumbar spine (LS) BMD was similar in groups A and B and was within normal limits. In contrast, femoral neck (FN) Z- and T-scores were significantly decreased in group B compared with group A (-0.68 +/- 0.14 vs -0.03 +/- 0.14 SD and -0.84 +/- 0.14 vs -0.22 +/- 0.14 SD, respectively; p < or = 0.002). Osteopenia (T-score between -1 and -2.5 SD) was present in 35% of group A and 43% of group B patients (NS). Osteoporosis (T-score < -2.5 SD) was detected in 7% of group B patients, but in none of those in group A (p = 0.05). In a longitudinal study, 56 subjects were evaluated at the time of alloBMT, and 33 and 23 were studied 6 or 12 months later, respectively (13 women, 20 men, 37.5 +/- 1.6 years). All were treated with supplements of calcium and vitamin D. Amenorrheic women received hormone replacement therapy (HRT). Three-monthly pamidronate infusions were given to 15 men and 10 non-amenorrheic women who were osteopenic/osteoporotic or had elevated baseline bone turnover markers. Mean baseline LS and FN Z- and T-scores were within normal range. Six months after BMT, FN BMD decreased by 4.2 +/- 0.7% (p < 0.001), and whole body BMD and bone mineral content by 1.5 +/- 0.4% and 3.1 +/- 0.6%, respectively (p < or = 0.0001). Twelve months after the graft, there was no further significant bone loss and only FN BMD decrease remained significantly different compared with baseline (-5.6 +/- 1.1%, p < or = 0.0001). These results indicate that the risk of decreased BMD is higher for the femoral neck than the lumbar spine and whole body levels in patients with allogeneic bone marrow transplantation, and that bone loss occurs mainly during the first 6 months after the graft.

Adolescent↗

Protein intake and bone disorders in the elderly.

Malnutrition, most notably protein deficiency, contributes to the occurrence of osteoporotic fractures not only by decreasing bone mass but also by altering muscle function. Furthermore, malnutrition is associated with increased morbidity in patients with osteoporotic fractures. The somatomedin system (IGF-1) may be directly involved in the pathogenesis of osteoporotic hip fractures and their complications in elderly patients. A low IGF-1 level is a risk factor for hip fracture. In subjects with appropriate intakes of vitamin D and calcium, giving protein supplements to correct an inadequate spontaneous protein intake increases circulating IGF-1 levels, improves clinical outcomes after hip fracture, and prevents bone mineral density loss at the proximal femur. Supplemental protein also significantly reduces the length of inpatient rehabilitation care. These data emphasize the importance of adequate nutrient intake in the prevention and treatment of osteoporotic fractures.

Age Distribution↗

Lower femoral neck bone mineral density in prepubertal former preterm girls.

The purpose of this case-control study was to determine bone mineral content and areal bone mineral density at various skeletal sites in former preterm girls, aged 7-9 years, and to compare these data with age-matched term controls. Subjects included 25 white, prepubertal, former preterm girls (gestational age 30.8 +/- 0.3 weeks, birthweight 1461 +/- 56 g [mean +/- SEM]). Controls included 50 healthy, white, prepubertal girls born at term and matched for age (two controls per case). Measurements included anthropometric variables, calcium intake according to a food-frequency questionnaire, bone mineral content (BMC; grams), and areal bone mineral density (aBMD; grams per square centimeter), using dual-energy X-ray absorptiometry (DXA) at six skeletal sites. Thirteen preterm girls and 13 age-matched term controls were reassessed 1 year after the first DXA measurement. The former preterm girls were similar to controls in terms of age and height, but were lighter (24.6 +/- 0.6 vs. 27.0 +/- 0.6 kg, p = 0.02). They also reported a higher median calcium intake (1058 vs. 759 mg/day, p = 0.004). aBMD was lower in former preterms compared with controls at the level of the radial metaphysis (0.283 +/- 0.006 vs. 0.298 +/- 0.004, p = 0.04), femoral neck (0.593 +/- 0.011 vs. 0.638 +/- 0.010, p = 0.007), and total hip (0.596 +/- 0.012 vs. 0.640 +/- 0.010, p = 0.007), but was similar between the two groups at the radial diaphysis (0.437 +/- 0.004 vs. 0.436 +/- 0.004) and femoral diaphysis (1.026 +/- 0.015 vs. 1.030 +/- 0.011). Femoral neck aBMD remained lower compared with controls in the subgroup of preterm girls reassessed after 1 year (0.608 +/- 0.017 vs. 0.672 +/- 0.020, p = 0.02). In random effects models for longitudinal data, taking into account the effects of age, weight, and height on aBMD (dependent variable), femoral neck aBMD remained lower in former preterms (p < 0.001). Prepubertal former preterm girls showed growth recovery, but had lower aBMD at the hip and radial metaphysis than age-matched term controls, despite spontaneously higher calcium intake. Preterm girls had similar aBMD results compared with controls at sites with predominantly cortical bone (radial and femoral diaphysis), which are known to be more sensitive to calcium intake.

Bone Density↗

Does the mini nutritional assessment predict hospitalization outcomes in older people?

BACKGROUND: the Mini Nutritional Assessment is a validated clinical tool for the assessment of nutritional status in older people. Moderate to severe malnutrition is common in elderly patients in hospital and is associated with a poor outcome. OBJECTIVES: to determine whether the Mini Nutritional Assessment can predict the outcome of hospital stay in older individuals. SETTING: a tertiary-care geriatric hospital. METHODS: we evaluated nutritional status using the Mini Nutritional Assessment in 1319 patients (mean age 84.2, 70% women) admitted between February 1996 and January 1998; 1145 complete assessments were available for analysis. The assessment was carried out on admission and studied in relation to length of stay and in-hospital mortality for all patients, and discharge to a nursing home for those living at home before admission. RESULTS: Mini Nutritional Assessment scores averaged 19.9+/-3.8 (mean+/-SD) with a range of 8.0-27.5, and a median of 20.5. A score below 17, corresponding to malnutrition, was associated with an almost threefold increase in mortality and in the rate of discharge to a nursing home; this contrasted with a score above 24, which indicates satisfactory nutritional status (11.3% vs 3.7%; P<0.01 and 20.3% vs 7.7%; P<0.001, respectively). Length of stay was longer in the low scoring group (42.0 days vs 30.5 days; P<0.0002). CONCLUSION: Poor nutritional status as measured by the Mini Nutritional Assessment was associated with increased in-hospital mortality, a higher rate of discharge to nursing homes and a longer length of stay.

Activities of Daily Living↗

Oligo-amenorrheic long-distance runners may lose more bone in spine than in femur.

PURPOSE: Strenuous training can be associated with amenorrhea leading to amenorrhea-related accelerated bone loss. Insufficient calorie energy, calcium, and/or protein intakes can also be frequently encountered in women with intense training, possibly contributing to bone loss. Long-distance runners with or without regular menses (age range 19-37 yr) were prospectively studied. METHODS: Changes in areal bone mineral density (BMD) were measured at 1-yr interval. RESULTS: Among 10 eumenorrheic, 11 oligo-amenorrheic, and 9 oral contraceptive users, there was no difference in energy, calcium, or protein intakes. Baseline BMD values were significantly lower in the oligo-amenorrheic group than in the two others at the level of lumbar spine (anteroposterior view: 0.941+/-0.039 in oligo-amenorrheic vs 1.077+/-0.029 or 1.051 +/-0.017 g x cm(-2), P < 0.005, in the eumenorrheic and contraceptive user groups, respectively) but not in weight-bearing bone such as proximal and midshaft femur. Over a 1-yr interval, during which the three groups did not differ in terms of running distances and dietary intakes, oligo-amenorrheic women displayed a significant decrease in lumbar spine BMD in lateral view (-0.049+/-0.012 in oligo-amenorrheic vs -0.001+/-0.013 and 0.014+/-0.012 g x cm(-2), p < 0.005, in the eumenorrheic and contraceptive user groups, respectively). We did not detect any significant change in femoral neck, trochanter, or midshaft BMD. CONCLUSIONS: Oligo-amenorrhea in long-distance runners, with adequate dietary intakes, was associated with a decrease in BMD affecting more the lumbar spine than the proximal and midshaft femur during a 1-yr follow-up.

Adult↗

Protein intake and bone growth.

Among osteotrophic nutrients, proteins play an important role in bone development, thereby influencing peak bone mass. Consequently, protein malnutrition during development can increase the risk of osteoporosis and of fragility fracture later in life. Both animal and human studies indicate that low protein intake can be detrimental for both the acquisition of bone mass during growth and its conservation during adulthood. Low protein intake impairs both the production and action of IGF-I (Insulin-like growth factor-I). IGF-I is an essential factor for bone longitudinal growth, as it stimulates proliferation and differentiation of chondrocytes in the epiphyseal plate, and also for bone formation. It can be considered as a key factor in the adjustments of calcium-phosphate metabolism required for normal skeletal development and bone mineralization during growth. In healthy children and adolescents, a positive association between the amount of ingested proteins and bone mass gain was observed in both sexes at the level of the lumbar spine, the proximal femur and the midfemoral shaft. This association appears to be particularly significant in prepubertal children. This suggests that, like for the bone response to either the intake of calcium or weight-bearing exercise, the skeleton would be particularly responsive to the protein intake during the years preceding the onset of pubertal maturation.

Animals↗

Hypoparathyroidism associated with aneurysm of the left subclavian artery (Kommerell's diverticulum) in an adult patient with a chromosome 22q11.2 deletion.

Hypoparathyroidism may either be acquired or of congenital origin. From the latter group, which represents a minority of cases, agenesis or hypoplasia of the parathyroid glands resulting in symptomatic hypocalcemia in the newborn or infant frequently is caused by a microdeletion of chromosome 22q11.2. We describe a man in whom hypoparathyroidism was first diagnosed at the age of 59 years. The endocrine disorder was found to be associated with this chromosome imbalance and also with an aneurysm of the left subclavian artery (Kommerell's diverticulum) compressing the esophagus and trachea. Given the potential implication for genetic counseling, a 22q11.2 deletion should be considered in the differential diagnosis of adult patients with hypoparathyroidism of unknown origin and should be searched for by appropriate molecular cytogenetic technique.

Chromosome Deletion↗

Osteoporosis, genetics and hormones.

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue. At a given age, bone mass results from the amount of bone acquired during growth, i.e. the peak bone mass (Bonjour et al., 1991, Theintz et al. 1992) minus the age-related bone loss which particularly accelerates after menopause. The rate and magnitude of bone mass gain during the pubertal years and of bone loss in later life may markedly differ from one skeletal site to another, as well as from one individual to another. Bone mass gain is mainly related to increases in bone size, that is in bone external dimensions, with minimal changes in bone microarchitecture. In contrast, postmenopausal and age-related decreases in bone mass result from thinning of both cortices and trabeculae, from perforation and eventually disappearance of the latter, leading to significant alterations of the bone microarchitecture (Fig. 1).

Bone Density↗

Osteoporosis in men.

Osteoporosis in men is becoming a public health problem. The complications of the disease that represent fractures are associated with higher mortality and morbidity in men than in women. In the management of the disease, the nurse plays a major role in the education and management of men with osteoporosis.

Aged↗

Evaluation of hormone replacement therapy use by the sales figures.

Despite the efficiency of hormone replacement therapy (HRT) to prevent climacteric manifestations and possibly the long-term deleterious influences of menopause, the prevalence of HRT is relatively low, and quite variable, depending on the population studied. Presently, there is no information regarding HRT in Switzerland and in the region of Geneva, which have particularly aged populations, with a life expectancy among the longest in the Western world. In this study, the number of women treated per year in 1993 and 1996, as well as the prevalence of HRT were estimated, based on the total amount of hormone preparations sold for HRT. In Switzerland, for a female population older than 45 years of about 1.45 million, the number of women on HRT was approximately 166,000 in 1993 and 202,000 in 1996. For Geneva, the female population was more than 86,000, and the number of treated women was about 14,000 and 21,000 in 1993 and 1996, respectively. Depending on the age class considered as susceptible of receiving HRT, the prevalence of this therapy may vary between 15 and 20% for Switzerland, and between 21 and 27% for Geneva in 1993. It was estimated between 17 and 24%, and 31 and 41% in 1996. These values are quite comparable to those reported for other countries with a similar socioeconomic level and obtained using different methods of evaluation.

Age Factors↗

Weekly administration of alendronate: rationale and plan for clinical assessment.

OBJECTIVE: This paper describes the rationale and supporting data for once-weekly dosing of alendronate. BACKGROUND: Alendronate sodium, a bisphosphonate that potently inhibits bone resorption, has been shown to increase bone mass and substantially reduce the incidence of osteoporotic fractures, including fractures of the hip. The standard regimen of daily administration has generally been well tolerated. However, weekly administration may provide greater convenience to patients without compromising efficacy or tolerability. The pharmacokinetics of alendronate and bone remodeling theory predict similar efficacy for weekly and daily administration if the cumulative dose is the same. Bone resorption in individual remodeling units normally proceeds for approximately 2 weeks; alendronate inhibits the rate and extent of resorption. Because the half-life of residence on bone surfaces is several weeks, weekly administration of alendronate should inhibit bone resorption to an overall extent similar to that of daily dosing, thereby producing similar effects on bone mass and strength. Animal studies demonstrate that both weekly and daily parenteral administration of alendronate effectively increase bone mass and strength, but confirmation of efficacy is needed for weekly oral dosing in humans. Although daily bisphosphonates (alendronate and risedronate) elicited esophageal irritation in a canine model of gastroesophageal reflux, weekly dosing with alendronate at a higher unit dose did not. Thus, the lower frequency of weekly dosing with a higher unit dose may actually reduce the risk of upper gastrointestinal irritation compared with daily administration of a lower dose. CONCLUSIONS: Current safety and efficacy data justify further investigation of once-weekly dosing of alendronate. Two positive-control, double-blind, randomized trials of osteoporosis treatment and prevention are currently being performed to assess the comparability of weekly, biweekly, and daily dosing of alendronate with regard to effects on bone density, safety, and tolerability.

Alendronate↗

Bone mineral density in lung-transplant recipients before and after graft: prevention of lumbar spine post-transplantation-accelerated bone loss by pamidronate.

BACKGROUND: Lung-transplant recipients are at risk of osteoporosis. They may have low bone mass even before posttransplantation immunosuppressive therapy. We studied bone mineral density (BMD) before and after lung transplantation and compared the efficacy of antiresorptive therapies to calcium and vitamin D supplementation. METHODS: Areal BMD was assessed in 42 patients awaiting lung transplantation and measured again after surgery at 6 (n = 29), and at 12 months (n = 20). Nineteen patients received antiresorptive therapy (30 mg pamidronate IV every 3 months (n = 14), or hormonal replacement therapy (n = 5)), and 10 patients received only calcium and vitamin D supplements. RESULTS: Mean age- and gender-adjusted lumbar spine (LS) and femoral neck (FN) BMD was significantly decreased prior to transplantation (- 0.6 +/- 0.2, p< 0.01, and - 1.5 +/- 0.2 standard deviation, p < 0.001, respectively). At that time, 29% were osteoporotic (T-score < - 2.5 below the peak bone mass), while 55% were below - 1.0 T-score. Antiresorptive therapy decreased the rate of LS bone loss during the first 6 months and led to a significant increase of BMD at 1 year, with LS changes of + 0.2 +/- 0.1 vs - 0.4 +/- 0.1 Z-score in the calcium-vitamin D group (p< 0.002), and + 0.2 +/- 0.1 vs - 0.04 +/- 0.1 for FN (NS). One out of 20 patients experienced clinically evident fractures during antiresorptive therapy, and 3 out of 12 in the calcium-vitamin D group. CONCLUSION: A significant proportion of patients awaiting lung transplantation was osteoporotic or osteopenic. Antiresorptive therapy (pamidronate or hormone-replacement therapy (HRT)) prevented accelerated LS bone loss after graft.

Adolescent↗

Markers of bone turnover for the management of patients with bone metastases from prostate cancer.

Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to that of bone formation in patients with bone metastases from prostate cancer before and after bisphosphonate treatment. Thirty-nine patients with prostate cancer and bone metastasis, nine patients with prostate cancer without bone metastases, nine patients with benign prostatic hyperplasia and 355 healthy age-matched men were included. Urinary non-isomerized (alpha CTX) and beta isomerized (beta CTX) type I collagen C-telopeptides (CTX) and a new assay for serum CTX were used to assess bone resorption. Bone formation was determined by serum osteocalcin, serum total (T-ALP) and bone (BAP) alkaline phosphatase and serum type I collagen C-terminal propeptide (PICP). Fourteen patients with bone metastases were also evaluated 15 days after a single injection of the bisphosphonate pamidronate (120 mg). Levels of all bone formation and bone resorption markers were significantly (P < 0.006-0.0001) higher in patients with prostate cancer and bone metastasis than in patients with benign prostatic hyperplasia, patients with prostate cancer without bone metastases and healthy controls. In patients with bone metastases the median was increased by 67% for serum osteocalcin, 128% for T-ALP, 138% for BAP, 79% for PICP, 220% for urinary alpha CTX, 149% for urinary beta CTX and 214% for serum CTX. After bisphosphonate treatment all three resorption markers significantly decreased by an average of 65% (P = 0.001), 71% (P = 0.0010) and 61% (P = 0.0015) for urinary alpha CTX, urinary beta CTX and serum CTX, respectively, whereas no significant change was observed for any bone formation markers. Patients with prostate cancer and bone metastases exhibit a marked increase in bone resorption, which decreases within a few days of treatment with pamidronate. These findings suggest that these new resorption markers may be useful for the management of these patients.

Aged↗

Dietary protein restriction lowers plasma insulin-like growth factor I (IGF-I), impairs cortical bone formation, and induces osteoblastic resistance to IGF-I in adult female rats.

Dietary protein deficiency, common in elderly, is associated with decreased areal bone mineral density and plasma insulin-like growth factor I (IGF-I). To investigate the early adaptation of bone cells to protein restriction, 6-month-old female rats were pair-fed with isocaloric 15% (control) or 2.5% casein diets for 14 days. Animals were then treated daily with rhIGF-I/IGFBP-3 (1:4, 2.5 mg IGF-I/kg BW) or with vehicle for 10 days. After double-labeling, proximal metaphysis and mid-diaphysis of the tibia were analyzed histomorphometrically. Plasma osteocalcin, IGF-I, and urinary deoxypyridinoline were quantified. After 14 days of protein restriction, significant drops in plasma osteocalcin (13%) and IGF-I (37%), in periosteal formation (83%) and mineral apposition (49%) rates are observed, indicating a decreased osteoblast recruitment and activity. In cancellous bone, a significant decrease in active eroded surfaces (27%) and osteoclast number (24%) indicates a transient depression of resorption. In rats fed the 15% casein diet, rhIGF-I/IGFBP-3 increases cancellous (42%) and periosteal (600%) formation rates, indicating an increased osteoblast recruitment. In protein-restricted rats, rhIGF-I/IGFBP-3 fails to increase cancellous or periosteal bone formation and plasma osteocalcin is significantly lower than in 15% casein+rhIGF-I/ IGFBP-3 rats. Protein restriction induces osteoblast resistance to rhIGF-I/IGFBP-3 in both bone envelopes. Low plasma IGF-I and osteoblast resistance to IGF-I, may contribute to the impaired periosteal formation.

Animals↗

Positive and negative control of the expression of parathyroid hormone (PTH)/PTH-related protein receptor via proximal promoter P3 in human osteoblast-like cells.

Three promoters, P1, P2, and P3, regulate the expression of the receptor for the human PTH/PTH -related protein. The P3 promoter, proximal to the gene, seems to be turned on in many tissues and to be the most active of the three in the human adult kidney. P3 is also active in human osteoblastic SaOS-2 cells. Its structure to function relationship is, however, still poorly understood. To address this issue we assayed, in transiently transfected SaOS-2 cells, the expression of reporter gene constructs containing truncated P3 promoter fragments and substitution mutants. We thus localized cis-acting elements essential for P3 promoter activity and identified two key Sp1 binding sites. We also found in the 5'-untranslated exon U4, transcribed from promoter P3, an element that inhibits the expression of the receptor and is not promoter specific. This study provides new insights into PTH receptor expression in human osteoblast-like cells.

5' Untranslated Regions↗