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Biomedical subjects

J R Zanchetta

Publications and source records attributed to J R Zanchetta.

At least 19 recordsLinked to original sources

Reduction in the risk of developing back pain persists at least 30 months after discontinuation of teriparatide treatment: a meta-analysis.

INTRODUCTION: Teriparatide [rhPTH (1-34)] reduces fracture risk, and in a published meta-analysis of clinical trials, teriparatide-treated patients had reduced incidence of back pain relative to placebo or to antiresorptive drugs. The aim of this study was to evaluate back pain in teriparatide-treated versus comparator-treated patients during an interval including controlled clinical trials plus 30 months of additional follow-up. METHODS: A meta-analysis of four completed randomized, double-blinded trials of teriparatide [rhPTH (1-34)] versus comparator was performed. A multivariate Cox proportional hazards model was used to assess the heterogeneity of results and to estimate the relative risk of back pain. RESULTS: Patients in the pooled teriparatide group had reduced risk for any back pain [relative risk, 0.73 (95% CI, 0.61-0.87)], moderate or severe back pain [0.72 (0.58-0.89)], and severe back pain [0.39 (0.25-0.61)] compared with pooled controls, from initiation of the study drug through the end of follow-up. Sensitivity analysis showed that the results were robust to the removal of each individual trial from the meta-analysis. Separate meta-analyses comparing teriparatide versus placebo or antiresorptive drugs gave similar results. CONCLUSIONS: Teriparatide-treated patients had a reduced incidence of back pain versus those receiving a comparator during an observation encompassing clinical trials plus 30 months of posttreatment observation.

Back Pain↗

[Relationship between renal function and bone mineral density in postmenopausal women that undergo bone mass evaluation].

As osteoporosis and renal insufficiency are two prevalent pathologies in the aging population we decided to evaluate retrospectively the renal function (estimated by formula) in postmenopausal women who came to our Institute for bone mass determination to establish the relationship between them. Thus, we studied 300 postmenopausal women with a mean age of 66.9 +/- 6.8 years who had a bone densitometry performed; we chose total femur bone mineral density (TFBMD) for defining osteopenia and osteoporosis as this measurement included substantial amounts of both trabecular and cortical bone; osteopenia/osteoporosis was diagnosed using T score criteria recommended by the WHO. We also measured BMD at the femoral neck. Renal function was estimated by the Cockcroft-Gault formula using serum creatinine determination. We found osteoporosis in 61 patients (20.3%). Of them, el 81.9% have renal insufficiency (estimated creatinine clearance-ECrC < or = 60 ml/min), compared to 54% of 239 women who had normal BMD/osteopenia (p < 0.001). Six of 61 (9.8%) women with osteoporosis had severe renal insufficiency (ECrC < or = 36 ml/min) versus 4/239 (1.6%) women with normal BMD/osteopenia (p = 0.001). Women with osteoporosis were older, and had a significantly lower weight and ECrC compared to patients without osteoporosis (ECrC 52 +/- 11 ml/min vs 59 +/- 12 ml/min; p < 0.0001). We found a significant positive correlation between TFBMD and ECrC (r = 0.389) as well as with weight (r = 0.422) and a negative correlation between age and ECrCE (r = -0.51) and with TFBMD (r = -0.22). In the multiple regression analysis only weight continued to correlate significantly with TFBMD (Beta = 0.344). When FNBMD was considered as the dependent variable, we found a significantly negative correlation with age (r = -0.30) and significantly positive correlations with height (r = 0. 16), weight (r = 0.33) and ECcr (r = 0.39). In the multiple regression analysis only age (Beta = -0.20) and weight (Beta = 0.20) continued having an independent correlation FNBMD. We conclude that our data confirm that there exists a substantial prevalence of renal insufficiency, even severe, among patients with densitometric osteoporosis that should be kept in mind when one is considering the prescription of medications as bisphosphonates that have renal clearance, so as not to jeopardize the efficacy and the security of these drugs.

Aged↗

The vacuum cleft sign: an uncommon radiological sign.

The intravertebral vacuum cleft sign (VCS) is an uncommon radiological sign, characterized by a radiolucent zone in the vertebral body. It is composed of 95% nitrogen and small amounts of oxygen and carbon dioxide. Post-traumatic ischemic necrosis could be its physiopathological mechanism, along with other pathologies like osteoporosis, corticosteroid therapy, diabetes, arteriosclerosis, alcoholism, multiple myeloma, bone metastasis and osteomyelitis. The broad diagnosis is made by antero-posterior X-ray, but computed tomography scan (CT scan) and magnetic resonance imaging (MRI) may help with the differential diagnosis. The aims of this paper are, on one hand, to communicate the clinical case of a 73-year-old osteoporotic woman with traumatic vertebral fractures who developed this sign in her radiological survey. On the other hand, its secondary aims are to review the medical literature about this sign and to show the clinical and radiological evolution after a percutaneous vertebroplasty.

Aged↗

Evaluation of cortical bone by peripheral quantitative computed tomography in renal transplant recipients.

BACKGROUND: The absolute risk of fractures in renal transplant patients is 3 times that of matched controls. Most of the symptomatic fractures are peripheral, suggesting a greater compromise of cortical bone. Peripheral quantitative computed tomography (pQCT) is a new imaging technique that allows separate noninvasive evaluations of cortical and trabecular bones. We investigated cortical bone by pQCT in 12 renal transplant patients (seven men and five women) for comparison with 27 normal controls. METHODS: pQCT (XCT 960, Stratec, Pforheim, Germany) was performed upon the distal radius of the nondominant forearm (15% the length of the ulna, proximal from the radius end plate). We evaluated total and cortical bone mineral density (TBMD, cBMD), total (cross-sectional) and cortical area (TA, cA), cortical thickness (cThk), endosteal and periosteal circumferences, and the buckling ratio (r/cThK). RESULTS: Compared with normal controls transplant patients as a whole showed a significant increase in TA, in endosteal circumference (P < .001), and in the buckling ratio (P < .001) with a significant reduction in cThK (P < .001). Female patients had a marked decrease in cA (51.4 vs 69.3 [pixel n]; P < .0001) and cThK (2.08 vs 2.78 mm; P < .0001). Male patients also had a decrease in cThK (2.54 vs 3.30 mm; P = .0001) and an increase in endosteal perimeter (31.2 vs 26.4 mm; P < .0001). Total time on dialysis prior to renal graft correlated negatively with cortical thickness (r = .62; P < .01). CONCLUSIONS: Our results suggest that a marked thinning of cortical bone may explain the increased incidence of peripheral fractures among renal transplant patients.

Adult↗

[Relationship between weight, body composition and bone mass in peritoneal dialysis].

Patients in chronic dialysis show a decrease in total bone mass. The factors that determine this decrease are not well known. In normal populations weight and its compartments are important determinants of bone mass. We studied total bone mineral content (TBMC), a measure of bone mass, and body composition using DEXA densitometry in 65 patients (45 females and 20 males) who had been in peritoneal dialysis for a mean of 40.3 +/- 23.2 months. Forty-eight patients (73.8%) had been previously in hemodialysis. The mean total time in dialysis for these patients was 76.8 months. As a group patients showed a very significant positive correlation between TBMC and weight, height, and lean body mass. A negative correlation was found between TBMC with the time in dialysis and iPTH. In men we found significant simple positive correlations between TBMC and weight, height and lean body mass. In women we found simple positive correlations of TBMC with weight, height and lean body mass and a negative correlation with iPTH. In the multiple regression analysis, lean body mass was the only body composition parameter that had a significantly positive correlation with TBMC in men; in women only height correlated positively with TBMC and iPTH continued to correlate negatively with bone mass. When we considered pre and postmenopausal women separately, bone mass was correlated positively with height and lean body mass and negatively with iPTH in postmenopausal women and only with height in pre-menopausal females. We conclude that the lean body mass compartment. is the most important component of weight that determines TBMC in peritoneal dialysis patients particularly in males and postmenopausal women. In postmenopausal women, secondary hyperparathyroidism seems to be particularly detrimental on bone mass.

Absorptiometry, Photon↗

Disintegration/dissolution profiles of copies of Fosamax (alendronate).

OBJECTIVE: Poor quality has been reported for some generics and other copies of original products. We performed a pilot study to compare the disintegration/dissolution profiles of FOSAMAX (alendronate) 70 mg tablets with those of copies of FOSAMAX that were manufactured outside the United States. RESEARCH DESIGN AND METHODS: We used the standard United States Pharmacopeia (USP) disintegration method to evaluate FOSAMAX 70 mg tablets and 13 copies. At least 12 (n = 12) dosage units were tested for each product (except Fosmin, n = 10). The dissolution profiles of FOSAMAX and one representative copy were also compared. RESULTS: Nine copies (Osteomax, Defixal, Fosmin, Endronax, Osteomix, Genalmen, Fixopan, Osteoplus, and Fosval) disintegrated two- to ten-fold faster than FOSAMAX. Three other copies (Neobon, Regenesis, and Ostenan) disintegrated at least five-fold slower than FOSAMAX. Neobon is a softgel capsule, so special consideration was given to this different dosage form. One copy (Arendal) did not fall into either category but exhibited potentially large inter- and intra-lot variability. Dissolution of alendronate from Regenesis lagged behind that from FOSAMAX. CONCLUSION: Slower disintegration may reduce efficacy because bisphosphonates must be taken in the fasting state and contact with food or even certain beverages severely reduces bioavailability. Faster disintegration (or the use of gel-caps or other alterations to the drug formulation) could increase the risk of esophagitis, an adverse event associated with prolonged contact of the esophagus with bisphosphonates. These disintegration and dissolution results suggest that important differences may exist between FOSAMAX and its copies with regard to bioavailability, pharmacokinetics, and clinical efficacy and safety profiles. Additional testing is warranted to evaluate the pharmacokinetics and clinical safety of these copies.

Alendronate↗

Effects of teriparatide [recombinant human parathyroid hormone (1-34)] on cortical bone in postmenopausal women with osteoporosis.

Treatment with teriparatide (rDNA origin) injection [teriparatide, recombinant human parathyroid hormone (1-34) [rhPTH(1-34)]] reduces the risk of vertebral and nonvertebral fragility fractures and increases cancellous bone mineral density in postmenopausal women with osteoporosis, but its effects on cortical bone are less well established. This cross-sectional study assessed parameters of cortical bone quality by peripheral quantitative computed tomography (pQCT) in the nondominant distal radius of 101 postmenopausal women with osteoporosis who were randomly allocated to once-daily, self-administered subcutaneous injections of placebo (n = 35) or teriparatide 20 microg (n = 38) or 40 microg (n = 28). We obtained measurements of moments of inertia, bone circumferences, bone mineral content, and bone area after a median of 18 months of treatment. The results were adjusted for age, height, and weight. Compared with placebo, patients treated with teriparatide 40 microg had significantly higher total bone mineral content, total and cortical bone areas, periosteal and endocortical circumferences, and axial and polar cross-sectional moments of inertia. Total bone mineral content, total and cortical bone areas, periosteal circumference, and polar cross-sectional moment of inertia were also significantly higher in the patients treated with teriparatide 20 microg compared with placebo. There were no differences in total bone mineral density, cortical thickness, cortical bone mineral density, or cortical bone mineral content among groups. In summary, once-daily administration of teriparatide induced beneficial changes in the structural architecture of the distal radial diaphysis consistent with increased mechanical strength without adverse effects on total bone mineral density or cortical bone mineral content.

Aged↗

Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.

BACKGROUND: Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown. METHODS: We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 microg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry. RESULTS: New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-microg and 40-microg parathyroid hormone groups; the respective relative risks of fracture in the 20-microg and 40-microg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragility fractures occurred in 6 percent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group (relative risk, 0.47 and 0.46, respectively [95 percent confidence intervals, 0.25 to 0.88 and 0.25 to 0.861). As compared with placebo, the 20-microg and 40-microg doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck; the 40-microg dose decreased bone mineral density at the shaft of the radius by 2 more percentage points. Both doses increased total-body bone mineral by 2 to 4 more percentage points than did placebo. Parathyroid hormone had only minor side effects (occasional nausea and headache). CONCLUSIONS: Treatment of postmenopausal osteoporosis with parathyroid hormone (1-34) decreases the risk of vertebral and nonvertebral fractures; increases vertebral, femoral, and total-body bone mineral density; and is well tolerated. The 40-microg dose increased bone mineral density more than the 20-microg dose but had similar effects on the risk of fracture and was more likely to have side effects.

Bone Density↗

Vitamin D and bone mineral density in ambulatory women living in Buenos Aires, Argentina.

The aim of this study was to determine possible associations between bone mineral density (BMD), 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (PTH). In a retrospective study we examined the case notes of free-living postmenopausal women living in our city (34 degrees S). We also report a low prevalence of vitamin D deficiency (25(OH)D < 25 nmol/1, 5.6%) and of secondary hyperparathyroidism (intact PTH > 65 pg/ml, 7.5%). Age was correlated with BMD at the lumbar spine (r = -0.25, p = 0.00038) and femoral neck (r = -0.252, p = 0.0003). Body mass index (BMI) was correlated with BMD at the femoral neck (r = 0.177, p = 0.021) but not at the lumbar spine. 25(OH)D was positively correlated with BMD at the femoral neck (r = 0.149, p = 0.036) but not at the lumbar spine. PTH was positively correlated with age (r = 0.279, p = 0.012) and negatively correlated with 25(OH)D (r = -0.322, p = 0.0036). PTH was also negatively correlated with BMD at the lumbar spine (r = -0.258, p = 0.02) and the femoral neck (r = -0.282, p = 0.011). Forward stepwise multiple regression showed that BMI, age and 25(OH)D made significant contributions to BMD at the femoral neck. PTH also showed a significant contribution to BMD at both sites. In conclusion, weak correlations found between PTH and 25(OH)D and BMD suggest these biochemical variables, among other factors, contribute to lumbar spine and femoral neck BMD.

Adult↗

Densitometric and tomographic analyses of musculoskeletal interactions in humans.

Previous studies with standard densitometry (DXA) have suggested that the bone mass is strongly dependent on the muscle mass in the species, following a similar relationship at any age and sex hormones or related factors potentiate that relationship. Studies with pQCT indicated that the surplus bone mass per unit of muscle mass previously observed in premenopausal women would be stored in skeletal regions with relatively little mechanical relevance, thus avoiding remotion through mechanically oriented remodelling by the bone mechanostat. Scanning the distal radius with pQCT has also showed a highly significant, linear relationship between SSI of the distal radius and the dynamometric maximal bending moment of the forearm in normal men and women. In order to investigate similar relationships in regions that are inaccessible to pQCT, we used spinal radiographs and axial QCT. This study affords additional evidence to the previous references concerning the direct, significant impact of the regional muscle strength on the determination of the tomographic indicators of bone mechanical quality and their indirect repercussion of the skeletal condition (curvature of the spine).

Journal Article↗

Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators.

CONTEXT: Raloxifene hydrochloride, a selective estrogen receptor modulator, prevents bone loss in postmenopausal women, but whether it reduces fracture risk in these women is not known. OBJECTIVE: To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures. DESIGN: The Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter, randomized, blinded, placebo-controlled trial. SETTING AND PARTICIPANTS: A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis. The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events. INTERVENTIONS: Participants were randomized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills; in addition, all women received supplemental calcium and cholecalciferol. MAIN OUTCOME MEASURES: Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained by interview at 6-month-interim visits. Bone mineral density was determined annually by dual-energy x-ray absorptiometry. RESULTS: At 36 months of the evaluable radiographs in 6828 women, 503 (7.4%) had at least 1 new vertebral fracture, including 10.1% of women receiving placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR], 0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95% CI, 0.4-0.7). Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture. Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1 for both raloxifene groups combined). Compared with placebo, raloxifene increased bone mineral density in the femoral neck by 2.1 % (60 mg) and 2.4% (120 mg) and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P<0.001 for all comparisons). Women receiving raloxifene had increased risk of venous thromboembolus vs placebo (RR, 3.1; 95% CI, 1.5-6.2). Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer. CONCLUSIONS: In postmenopausal women with osteoporosis, raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture.

Adult↗

Calcium bioavailability and parathyroid hormone acute changes after oral intake of dairy and nondairy products in healthy volunteers.

This study was designed to compare calcium bioavailability and serum parathyroid hormone acute changes after oral intake of 500 mg of elemental calcium from liquid milk, yogurt, calcium-citrate-enriched powdered milk or a calcium carbonate pill; or after intake of soybean imitation-milk. After a 12-h fast, blood samples were drawn both at baseline and 1, 2, 3 and 4 h after an oral intake of the above-mentioned products, which were ingested together with a light neutral breakfast. The administration order of the study products was randomly assigned to each of 19 healthy young volunteers (11 females, 8 males). The baseline serum concentrations of ionized calcium, phosphorus and intact parathyroid hormone (iPTH) were normal. Calcium-citrate-enriched powdered milk induced a significant increase in serum ionized calcium (p<0.001) and a significant and continuous decrease in serum iPTH concentration (p<0. 001). Yogurt and the calcium carbonate pill induced a similar but less significant effect, increasing serum ionized calcium (p<0.05) and decreasing serum iPTH (p<0.01). Liquid milk only induced a significant change in serum ionized calcium and iPTH concentration during the first 2 h; this effect was lost during the following 2 h. In conclusion, our study suggests the possibility that the addition of calcium citrate to powered milk may improve calcium bioavailability and enhance the inhibitory effect on serum iPTH in the assayed conditions.

Adult↗

[Metabolic changes in 2612 patients with nephrolithiasis].

Nephrolithiasis is one of the most frequent pathologies of the urinary tract. Its prevalence in the city of Buenos Aires is 4%. Different biochemical and physiological disturbances may create an environment conductive to renal stone formation. We present the results of an ambulatory evaluation in 2612 patients for the purpose of updating the classification of nephrolithiasis. An abnormal urinary biochemistry was observed in 2423 patients (92.8%) that could be classified in 15 categories. A single diagnosis was documented in 61.5% of the patients, and the remaining 31.2% had more than one diagnosis (concurrent abnormalities). No abnormality was found in 189 stone formers (7.2%). Idiopathic hypercalciuria was the most frequent abnormality, it was encountered in 31.2%; hyperuricosuria and gouty diathesis (presence of urine pH < 5.5, with normal or high uricemia) accounted for 9.4% and 5.4% of patients, respectively. On the other hand, hypomagnesuria affected 6.7% of the stone formers and hypocitraturia was observed in 4.5%. Primary hyperparathiriodism, hyperoxaluria and cystinuria were seen less frequently in 2.6%, 1.3 and 0.45% of patients. Low urine volume was found in 12% of the patients. Among those patients with more than one abnormality, we found that hypercalciuria together with hyperuricosuria and hypocitraturia (12%) was the prevalent association followed by hypercalciuria with hyperuricosuria (9.1%). Our results show the importance of studying nephrolithiasis patients from a biochemical point of view, since this is the only way to achieve a diagnosis of the metabolic abnormality and introduce a specific therapy to prevent recurrence.

Adult↗

[Vitamin D status in women living in Buenos Aires].

Bone loss has both age-related and menopausal components. The causes of age-related bone loss are multifactorial. In order to establish vitamin D status in women in our city (34 degrees S), calcidiol levels were assessed in 357 ambulatory women aged 40-90 years. One hundred and eighty were evaluated during summer time and 177 during winter time. We also evaluated intact PTH values in a subgroup of 231 women and this allowed us to document the prevalence of secondary hyperparathyroidism. Summer levels of calcidiol were significantly higher than in winter: 25.3 +/- 8.5 vs 21.3 +/- 7.4 ng/ml (p < 0.001). We found 4.4% of calcidiol levels < 10 ng/ml (2.2% in summer and 6.6% in winter). Prevalence of calcidiol between 10-20 ng/ml reached 67% in winter and went down to 25% during summer. Prevalence of secondary hyperparathyroidism was 5.2%. Even though prevalence of vitamin D deficiency was low, a great proportion of ambulatory women had calcidiol levels between 10-20 ng/ml. These values would not be sufficient for elderly people and could result in increased calcium mobilisation and further bone loss.

Adult↗

Gender-related differences in the relationship between densitometric values of whole-body bone mineral content and lean body mass in humans between 2 and 87 years of age.

The mineral, lean, and fat contents of the human body may be not only allometrically but also functionally associated. This report evaluates the influence of muscle mass on bone mass and its age-related changes by investigating these and other variables in both genders in the different stages of reproductive life. We have analyzed the dual-energy X-ray absorptiometry (DEXA)-determined whole-body mineral content (TBMC), lean body mass (LBM), and fat body mass data (FBM) of 778 children and adolescents of both genders, aged 2-20 years [previously reported in Bone 16(Suppl.): 393S-399S; 1995], and of 672 age-matched men and women, aged 20-87 years. Bone mass (as assessed by TBMC) was found to be closely and linearly associated with muscle mass (as reflected by LBM) throughout life. This relationship was similar in slope and intercept in prepubertal boys and girls. However, while keeping the same slope of that relationship (50-54 g increase in TBMC per kilogram LBM): (1) both men and women stored more mineral per unit of LBM within the reproductive period than before puberty (13%-29% and 33%-58%, respectively); (2) women stored more mineral than age-matched men with comparable LBM (17%-29%) until menopause; and (3) postmenopausal women had lower values of bone mineral than premenopausal women, similar to those of men with comparable LBM. Men showed no age effect on the TBMC/LBM relationship after puberty. Multiple regression analyses showed that not only the LBM, but also the FBM and body height (but not body weight), influenced the TBMC, in that decreasing order of determining power. However, neither the FBM nor body height could explain the pre/postpubertal and the gender-related differences in the TBMC/LBM relationship. Accordingly: (1) calculated TBMC/LBM and FBM-adjusted TBMC/LBM ratios were lower in girls and boys from 2-4 years of age until puberty; (2) thereafter, females rapidly reached significantly higher ratios than age-matched men until menopause; and (3) then, ratios for women and age-matched men tended to equalize. A biomechanical explanation of those differences is suggested. Sex hormones or related factors could affect the threshold of the feedback system that controls bone remodeling to adapt bone structure to the strains derived from customary mechanical usage in each region of the skeleton (bone "mechanostat"). Questions concerning whether the mineral accumulation in women during the reproductive period is related or not to an eventual role in pregnancy or lactation, or whether the new bone is stored in mechanically optimal or less optimal regions of the skeleton, are open to discussion.

Absorptiometry, Photon↗

[Experimental effects of olpadronate and pamidronate on bone mass].

Ovariectomy and immobilization in rats have demonstrated to be useful models for osteopenia and they are considered to mimic some aspects of human osteoporosis associated with a deficit of ovarian hormones and the absence of mechanical function (disuse of the bone). Pamidronate (APD) and Olpadronate (OLPA), a new dimethylated aminobisphosphonate, on a continuous oral scheme (APD: 8 and OLPA: 0.8 mg/kg/day) or on an intermittent parenteral scheme (APD: 1.25 and OLPA: 0.075 mg/kg every 15 days) did effectively prevent the trabecular bone loss caused by immobilization (unilateral sciaticectomy), by lack of ovarian stimuli (bilateral ovariectomy) or by both approaches. There were no signs of deterioration in the cortical bone mass. In a model of preestablished osteopenia, caused by estrogen deprivation, OLPA stopped the progression of the bone mass loss (0.5 mg/kg/i.v. every 15 days) and restored (0.30-0.60 mg/kg/i.v. every 15 days) the bone mineral density which had been affected (trabecular and cortical). The different activity of OLPA and APD on trabecular and cortical regions of long bones seems to accompany their different responses because of negative stimulus: better responses were more evident in the trabecular bone which proved to be more labile. In these "in vivo" models of OLPA's efficacy was similar to APD's but it was roughly 5-10 times more potent. OLPA has a high safety margin. Therefore, it could advantageously be used in those bone diseases which benefit with the use of bisphosphonates.

Analysis of Variance↗