alendronate, Fosamax
Curative effect of combined treatment with alendronate and 1 alpha-hydroxyvitamin D3 on bone loss by ovariectomy in aged rats.

Ito M, Azuma Y, Takagi H, Komoriya K, Ohta T, Kawaguchi H.

Pharmacological Research Department, Teijin Institute for Bio-medical Research, Teijin Ltd., Hino, Tokyo, Japan. masa.itou teijin.co.jp

We investigated the combined effects of alendronate and 1alpha-hydroxyvitamin D3 (1alpha(OH)D3) on the bone mass and strength in aged ovariectomized rats and compared them with those of single treatments. Forty-week-old female rats underwent ovariectomy or sham operation, and after 15 weeks, ovariectomized rats were daily administered vehicle alone, alendronate (0.2 or 1.0 mg/kg,p.o.), 1alpha(OH)D3 (0.02 microg/kg, p.o.), or the combinations of 0.2 or 1.0 mg/kg of alendronate and 1alpha(OH)D3. After 12 weeks, the groups receiving combined treatments had significantly increased bone density and mechanical strength of the 4th lumbar vertebral body and the midfemur compared to the vehicle-treated group, and the effects were almost equal to or slightly less than the addition of those of the respective single treatments. The increase in mechanical strength was proportional to that in bone mineral density, suggesting that the stimulatory effects of these treatments on bone strength are ascribable primarily to those on bone mass. Analyses of histology, computed tomography, and biochemical markers confirmed the strong effect of the combined treatment on trabecular bone in particular, which was associated with increased trabecular number and decreased bone turnover. We propose that the combination of daily alendronate and 1alpha(OH)D3 is clinically promising as a curative treatment of established postmenopausal osteoporosis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12184731&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
The values of urinary NTx in postmenopausal women undergoing HRT; the role of additional alendronate therapy.

Posaci C, Altunyurt S, Islekel H, Saygili U, Altekin E, Onvural A, Onvural B.

Department of Obstetrics and Gynecology, Dokuz Eylul University, Faculty of Medicine, 35340 Inciralti, Izmir, Turkey.

OBJECTIVE: To determine the changes in levels of urinary NTx at the end of the 6th month of oral and transdermal hormone replacement therapy (HRT) and the effects of additional alendronate therapy for osteoporotic women. METHOD: Of 66 postmenopausal women 23 were treated with oral estradiol+norethisterone acetate (E+P), and 22 were treated with transdermal estradiol+norethisterone acetate. The third group consisted of 21 women with osteoporosis (bone mineral density < 100 mg/cm(3)) and treated with oral E+P plus alendronate 10 mg/day. RESULT: Significant decreases of urinary NTx levels were seen after HRT in all study groups (P < 0.05). But the decline of NTx levels was not different between the oral and transdermal HRT groups (P > 0.05). There was no additional decrease in the levels of NTx with alendronate therapy (P > 0.05) but NTx excretion diminished more in patients with high baseline levels. CONCLUSION: The decline of NTx at the end of the 6th month of HRT reflects the decrease of bone resorption and it is not related to the route of administration. Copyright 2002 Elsevier Science Ireland Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12191850&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
[A study of the safety of rapid infusion of alendronate]

[Article in Japanese]

Oura S, Sakurai T, Yoshimura G, Tamaki T, Umemura T, Kokawa Y.

Dept. of Surgery, Wakayama Medical College Kihoku Hospital.

To investigate the safety of rapid infusion of alendronate, we used alendronate therapy for 11 breast cancer patients with bone metastasis. Of the 11 patients, only 1 had hypercalcemia and the remaining 10 normocalcemia. Rapid infusion of alendronate consisted of an administration of alendronate 10 mg diluted in 100 ml saline in 30 minutes, and was repeated every two weeks. Each patient underwent 1 to 9 alendronate treatments. During alendronate therapy, only one patient complained of general fatigue, and the remaining 10 showed no alendronate-induced clinical symptoms. Rapid infusion of alendronate caused an increase in BUN level in two patients receiving intravenous hyperalimentation (IVH), a mild increase of GOT level in one, and a decrease of serum phosphorus level in two receiving IVH. However, no increase was found in serum creatinine and GOT levels. In addition, no patients showed alendronate-induced hypocalcemia. In conclusion, rapid infusion of alendronate brings about no major adverse effects, and makes it easier for many patients with bone metastasis to receive alendronate therapy on an outpatient basis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10065098&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Use of alendronate in peri-implant defect regeneration.

Meraw SJ, Reeve CM, Wollan PC.

Department of Dental Specialties, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.

BACKGROUND: Previous studies have demonstrated an increase in bone mass and density with use of systemic alendronate sodium. This agent acts as an inhibitor of osteoclast activity, and is thought to result in more net osteoblastic activity. The objective of this study was to determine the effects of locally applied alendronate sodium on guided bone regeneration around dental implants. METHODS: Six adult mongrel dogs were divided into 2 groups: one group received alendronate-coated dental implants, and the other group served as control. Two types of dental implants were used in each dog: hydroxyapatite (HA)-coated and titanium machine-polished (TMP), for a total of 4 groups. Dental implants were placed immediately after extraction of the right and left second, third, and fourth mandibular premolars; a resorbable collagen membrane was secured over the implants and defects; and the flaps were closed primarily. Fluorescent labels were administered intravenously on days 0, 6, 12, and 22 to measure bone formation rate. Dogs were sacrificed on day 28. The specimens were sectioned and mounted, and bone formation rate was recorded with a computerized microscopic digitizer. Specimens were stained with Stevenel's blue and van Gieson's picric fuchsin. Bone-to-implant contact was recorded with a computerized microscopic digitizer. RESULTS: The results indicated a significant effect of locally applied alendronate (P < 0.0001) with both types of implants (HA and TMP), as well as the HA coating (P< 0.02) on increased bone formation rate. Additionally, alendronate had a significant effect on bone-to-implant contact, with an increase in the TMP model (P < 0.0001) and a decrease in the HA model (P < 0.0001 ). HA coating also had a significant effect on increasing bone-to-implant contact (P < 0.04). CONCLUSIONS: The results indicate that alendronate increases early bone formation rate around dental implants. Additionally, the local application as described resulted in greater bone-to-implant contact with TMP implants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10102552&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Alendronate affects long bone length and growth plate morphology in the oim mouse model for Osteogenesis Imperfecta.

Evans KD, Lau ST, Oberbauer AM, Martin RB.

Department of Animal Science, University of California, Davis, 2251 Meyer Hall, One Shields Avenue, Davis, CA 95616, USA.

Alendronate, a bisphosphonate drug, has shown promise in reducing remodeling and bone loss in postmenopausal osteoporosis. Alendronate acts directly on the osteoclast, inhibiting its resorption capability. This inhibition of osteoclast activity has led to the use of bisphosphonates in the treatment of the osteogenesis imperfecta condition. Treatment of osteogenesis imperfecta with bisphosphonates enhances bone strength, but the consequences on linear bone growth are not well defined. Using the oim mouse model for type III osteogenesis imperfecta, two doses of alendronate, low (0.125 mg/kg/wk) and high (2.5 mg/kg/wk) were administered weekly via intraperitoneal injection starting at 4 weeks of age and ending at 12 weeks of age to assess the effects of alendronate on humerus and ulna length. The higher dose of alendronate reduced humerus and ulna length in the oim/wt and wt/wt genotypes for both sexes (P < 0.05). The oim/oim humerus and ulna were not significantly affected by the higher dose of alendronate in females, but reduced bone length in males (P < 0.0085). Proximal humerus growth plate area was affected by both genotype and alendronate dose and growth plate diameter was increased at the chondro-osseous junction by both alendronate doses (P < 0.011). Genotype and alendronate dose affected growth plate height. The oim/oim genotype displayed taller growth plates. The high dosage of alendronate increased overall growth plate height, particularly within the hypertrophic zone, which suggests a failure of vascular invasion-induced apoptosis in the hypertrophic cells. In conclusion, these results indicate that high doses of alendronate (>2.5 mg/kg/wk) inhibit long bone length in mice through alteration of the growth plate and possibly reduced resorption at the chondro-osseous junction.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12667554&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Alendronate did not inhibit instability-induced bone resorption. A study in rats.

Astrand J, Aspenberg P.

Department of Orthopedics, Lund University Hospital, Sweden. Jorgen.Astrand ort.lu.se

Alendronate is a bisphosphonate that can decrease osteoclastic activity. It has been suggested as treatment for periprosthetic osteolysis. We used 48 rats, of which 32 had a plate implant on one tibia, to study the effect of alendronate on bone resorption at an unstable implant-bone interface. The plate has a handle on top, which can be grasped through the skin and turned, to create a sliding motion of a titanium surface against the underlying bone. This is known to result in bone resorption, which was studied by histomorphometry. Osmotic minipumps were used to administer alendronate at 0.063 mg/kg/day or saline. The systemic effect of the treatment was assessed by ashing the proximal metaphyses of the tibia of the contralateral unoperated leg. The ash-weight was increased in the alendronate-treated group by 43% (p = 0.0001), corresponding to histological changes in the metaphyseal bone. There was no inhibition of the instability-induced bone resorption at the test surface by alendronate: bone was being resorbed and replaced by a tissue similar to a loosening membrane.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10191752&dopt=Abstract alendronate Fosamax