alendronate, Fosamax
Effect of discontinuation of alendronate treatment and exercise on bone mass and physical fitness: 15-month follow-up of a randomized, controlled trial.

Uusi-Rasi K, Sievanen H, Heinonen A, Kannus P, Vuori I.

UKK Institute for Health Promotion Research, FIN-33501 Tampere, Finland. kirsti.uusi-rasi uta.fi

The purpose of this study was to evaluate the remaining effects of 12-month intervention of alendronate and exercise on selected risk factors of fragility fractures in 15-month follow-up after withdrawal of intervention among early postmenopausal women. The trial consisted four experimental groups: (1) 5 mg of alendronate daily + exercise (Al+Ex+), (2) 5 mg alendronate daily (Al+Ex-), (3) placebo + exercise (Al-Ex+), and (4) placebo (Al-Ex-). At the follow-up measurements, bone mass and physical fitness of 102 women (mean age 53.5 +/- 2.5 years) out of initial 150 subjects could be evaluated. Alendronate increased bone mass significantly [mean; 95% confidence interval (CI)] during the intervention at the lumbar spine (3.9%; 2.2% to 5.7%) and femoral neck (2.1%; 0.9% to 3.4%). After withdrawal of alendronate, bone loss resumed to the rate comparable to that evident in the placebo group. Despite the declining bone mass, the between-group mean difference (3.2%; 1.0% to 5.4%) remained at the lumbar spine. However, the benefits at the femoral neck had disappeared 15 months after the withdrawal of alendronate. The 12-month exercise training resulted in significant increases in muscle power, dynamic balance, and aerobic capacity with no benefits on bone mass. Fifteen months later, these performance variables had declined among both the exercisers and nonexercisers. Although the between-group differences were no longer statistically significant, muscle power, dynamic balance, and aerobic capacity of those who exercised still remained above the pretraining levels. In conclusion, 12-month treatment with alendronate prevented postmenopausal bone loss, and residual effect was seen 15 months after withdrawal of the drug at the lumbar spine. Similarly, exercise improved muscle power, agility, and aerobic capacity during the intervention, but the improvement was lost after the cessation of the exercise program. Based on these results, it was evident that to maintain the benefits of alendronate or exercise, therapy should be continued.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15336619&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
The NTX assay in the follow-up of the osteoporotic patients: 3 years of alendronate treatment.

Maugeri D, Speciale S, Santangelo A, Curasi' MP, Calanna A, Bonanno MR, Barbagallo P, Motta M, Malaguarnera M, Panebianco P.

Institute of Internal Medicine and Geriatrics, Catania University, Via Messina 829, I-95126 Catania, Italy.

These studies were conducted on 38 female patients treated with alendronate (10 mg/day, per os) for 3 years, because of osteoporosis. Of these patients, 29 were in the menopausal age longer than 10 years, and the remaining nine patients were in menopausa shorter than 10 years. Urine sample were taken at the start of the treatment and every 6 months afterward for 3 years, and crosslinked N-telopeptides of type I collagen (NTx) have been measured in them by means of an ELISA technique. Bone mineral density (BMD) has been recorded at the ultradistal (UDBMD) and mediodistal (MDBMD) region of radius of the non-dominant side. Body mass index (BMI) of the subjects has also been determined each time. The baseline values of NTx varied very much, scattered in a range of 11-215 nanomoles bone collagen equivalent/millimoles creatinine (nM BCE/mM Cr), in average 59+/-46; those of UDBMD and MDBMD amounted to 258+/-63 and 587+/-112 mg/cm(2), respectively. NTx, the BMD values and the menopausal age does not correlate with cach other. Both BMD values increased almost linearly in the total study pool during the 3-years-long treatment, being 3.0-9.2 and 0.8-2.5% higher in terms of UDBMD and MDBMD, respectively. Urine NTx concentrations decreased during the same time 30-35%. It is concluded that monitoring of urine NTx levels may be very useful during antiosteoporotic treatments, because a reduction of NTx is an indicator of the slowing down of bone turnover and the bone losses, as was observed during the alendronate therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15374056&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Meta-analysis of the efficacy of alendronate for the prevention of hip fractures in postmenopausal women.

Papapoulos SE, Quandt SA, Liberman UA, Hochberg MC, Thompson DE.

Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.

Treatment with alendronate, a potent and specific inhibitor of bone resorption, is known to significantly reduce fracture risk among women with postmenopausal osteoporosis. The purpose of this meta-analysis was to assess the consistency of the effect of alendronate in reducing the risk of hip fracture among different studies and populations. Data from completed, randomized, treatment studies were pooled in a meta-analysis. The duration of the studies ranged from 1-4.5 years. The dose of alendronate ranged from 5-20 mg/day, with over 95% of patients receiving either 5 or 10 mg/day during the trials. In patients with a T-score of less than or equal to -2.0, or with a vertebral fracture, the effect on hip fracture risk consistently favored patients receiving alendronate therapy, with an overall reduction in risk of hip fracture of 45% [95% confidence interval (CI) 16% to 64%, P=0.007]. For patients who met the criteria of osteoporosis, as defined by the World Health Organization (WHO), the overall risk reduction was 55% (95% CI 29% to 72%, P=0.0008). In both analyses we performed a sensitivity analysis by removing one study at a time. The strength of the evidence was not dependent on any one study. We conclude that therapy with alendronate is associated with significant and clinically important reductions in the incidence of hip fracture in women with postmenopausal osteoporosis. The overall reduction is consistent among different patient populations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15448985&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Effects of short-term alendronate treatment on the three-dimensional microstructural, physical, and mechanical properties of dog trabecular bone.

Hu JH, Ding M, Soballe K, Bechtold JE, Danielsen CC, Day JS, Hvid I.

Orthopaedic Research Laboratory, Department of Orthopaedics, Aarhus University Hospital, Denmark.

The bisphosphonate, alendronate, is well known for its potent inhibition of osteoclast-mediated bone resorption. It has been used clinically for the treatment of osteoporosis and has also recently been used to reduce osteolysis around prostheses in a canine revision model of implant loosening (femoral condyle). In this study, the effects of alendronate on trabecular bone properties were assessed in dogs at an oral dose of 0.5 mg/kg per day over a 12 week period, and compared with control dogs. Cubic cancellous bone specimens were produced from lumbar vertebrae (L-1 and L-2) and bilateral proximal humeri. These specimens were scanned using a high-resolution microcomputed tomography (micro-CT) system. From accurate data sets, three-dimensional microstructural properties were calculated and physical and mechanical properties were determined. Treatment with alendronate increased bone volume fraction by 9.5%, 7.7%, 7.4%, and 18.4%, respectively, in L-1, L-2, humeral greater tuberosity, and humeral head trabecular bone. In the lumbar vertebrae, the alendronate-treated trabeculae were thicker and lower in bone surface-to-volume ratio. In the greater tuberosity, the alendronate-treated trabeculae were thicker, lower in bone surface-to-volume ratio, and less anisotropic. In the humeral head, the alendronate-treated trabeculae were thicker, less anisotropic, lower in surface density, and showed decreased trabecular separation. Alendronate significantly increased apparent density and collagen density in the lumbar vertebrae and humeral heads, and significantly decreased collagen concentration in the vertebrae. In the lumbar vertebrae, Young's modulus in the cephalocaudal direction, ultimate stress, and failure energy were significantly increased in the alendronate-treated group. The changes in mechanical properties in the humeral head trabecular bone were similar to those seen in the lumbar vertebrae. Our results demonstrate that alendronate increases the mechanical properties of healthy canine trabecular bone after short-term treatment. The physical and microstructural changes of trabecular bone are consistent with the significantly increased mechanical properties.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12477573&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Alendronate reduces serum TNFalpha and IL-1beta, increases neutrophil counts, and improves bone mineral density and bone metabolism indices in patients with chronic idiopathic neutropenia (CIN)-associated osteopenia/osteoporosis.

Papadaki HA, Tsatsanis C, Christoforidou A, Malliaraki N, Psyllaki M, Pontikoglou C, Miliaki M, Margioris AN, Eliopoulos GD.

Department of Hematology University of Crete School of Medicine, University Hospital of Heraklion, P.O. Box 1352, Heraklion, Crete, Greece.

The current study was undertaken to investigate the effect of alendronate on bone mineral density (BMD), bone metabolism markers, and serum bone-resorbing cytokines in patients with chronic idiopathic neutropenia (CIN)-associated osteopenia/osteoporosis. Sixteen randomly selected women, 7 with CIN-associated osteoporosis and 9 with CIN-associated osteopenia, and 14 age- and menopausal status-matched healthy volunteers, were enrolled in the study. Patients received 10 mg alendronate daily per os for 360 days and studies were done before treatment (day 0) and at varying time points during the study. We found that patients' BMD measurements increased by 5.32% after treatment, and that the elevated serum osteocalcin (OC), a bone formation marker, decreased by day 30, normalized by day 90, and increased again by day 270 of treatment. Elevated values of patients' urine deoxypyridinoline (Dpd) and N-telopeptide of type I of collagen (NTx), two bone resorption markers, returned to the control range by day 30 and decreased thereafter. Increased levels of patients' serum tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta), two bone resorbing cytokines, returned to the control range by day 30 and decreased thereafter. Peripheral blood neutrophil counts increased by day 30 and continued to rise thereafter, reaching a mean value higher than 2650 neutrophils per microl of blood on day 360. Interestingly, alendronate-induced changes in the levels of both cytokines correlated inversely with the respective changes in neutrophil counts and BMD measurements, and positively with the changes in the respective means of urine NTx and Dpd values. All these findings indicate that alendronate is effective in treating CIN-associated osteopenia/osteoporosis, and that the beneficial effect of the compound may lie, at least in part, in its property to inhibit the production of TNFalpha and IL-1beta by cells of the monocyte/macrophage system, in which osteoclasts are included. Copyright 2004 Springer-Verlag

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15490268&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Effects of alendronate on restoration of biomechanical properties of periodontium in replanted rat molars.

Shibata T, Komatsu K, Shimada A, Shimoda S, Oida S, Kawasaki K, Chiba M.

Department of Pharmacology, School of Dental Medicine, Tsurumi University, Tsurumi-ku, Yokohama, Japan. shibata-t tsurumi-u.ac.jp

OBJECTIVE: We examined the effect of the pretreatment of roots with alendronate on the restoration of the support function of the healing periodontal ligament in replanted rat molars. METHODS: The left maxillary first molars were extracted, placed in 0.9% NaCl containing 1 mm alendronate (alendronate group) or 0.9% NaCl (control group) for 5 min, and were replanted into their sockets. Groups of animals were killed at 7, 14, and 21 days after replantation. Normal control rats were also killed on the same days. The force required to extract the replanted or normal tooth from its socket was measured, and a load-deformation curve was developed and analyzed. Micro-computed tomography and histologic analyses were also made. RESULTS: The mechanical properties of the healing periodontal ligament in the alendronate group were gradually restored from 7 to 21 days. However, fractures of the roots and bones during mechanical testing occurred in most of the replanted teeth in the control group at 21 days. The rates of restoration of the mechanical strength, extensibility, stiffness, and toughness for the alendronate group at 21 days were 67, 98, 74, and 68% of the normal controls, respectively. Micro-computed tomography and histologic observations revealed that bone-like structures within the pulp and ankylosis between the roots and socket bones occurred commonly in the control group, but were uncommon in the alendronate group. CONCLUSIONS: Our findings suggest that the pretreatment with alendronate inhibits the formation of abnormal mineralized tissues and results in better restoration of the support function of the healing periodontal ligament in replanted teeth. (c)Blackwell Munksgaard 2004

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15491345&dopt=Abstract alendronate Fosamax