alendronate, Fosamax
An opportunity for medication risk reduction, healthcare provider collaboration, and improved patient care: a retrospective analysis of osteoporosis management.

Bernett GB, Feldman S, Martin H, Smith BC, Raineri BD.

Genesis Health Ventures, Kennett Square, Pennsylvania, USA.

OBJECTIVES: The objectives of this study were to examine the degree to which long-term care providers are compliant with product labeling regarding administration of alendronate in patients with renal insufficiency and presence of, or predisposition to, upper gastrointestinal disorders; and to observe differences, if any, in prescribing patterns between alendronate and calcitonin-salmon nasal spray in skilled nursing facilities. STUDY DESIGN: We studied retrospectively analyzed patient charts, including medication histories and laboratory data. SETTING: Our study comprised 134 skilled nursing facilities from 21 states. PARTICIPANTS: We studied postmenopausal women, age > or =65 years, receiving either alendronate or calcitonin-salmon nasal spray for a minimum of 2 weeks. MEASUREMENTS: Consultant pharmacists reviewed resident charts submitted the following data for each resident: 2-week history of alendronate or calcitonin use, 2-week history of H2 receptor antagonist or proton pump inhibitor use, most recently documented serum creatinine, actual body weight, and date of birth. RESULTS: Of 905 subjects in the analysis, 38.5% (n = 348) did not have documentation of serum creatinine. Of the 267 alendronate patients for whom creatinine clearance could be calculated, more than half had renal insufficiencies of creatinine clearance <35 mL/min/1.73 m(2) (51.3%, n = 137). In addition, despite widespread information regarding caution in using alendronate in patients with upper gastrointestinal disorders, we found that 33.9% (n = 151) of all alendronate patients were concurrently receiving either H2 receptor antagonists or proton pump inhibitors. Although similar results were observed in the residents taking calcitonin, that agent has no precautions regarding its use in the renally impaired or in patients with gastrointestinal disorders. CONCLUSION: Data from this study indicate that long-term care clinicians might not be adequately differentiating patient profiles and safety criteria when initiating residents on osteoporosis pharmacotherapy, as evidenced by similar prescribing trends in both the alendronate and calcitonin groups. Given its package insert's statements regarding use of alendronate in the renally compromised, results from the alendronate group were particularly problematic as a result of the large number of residents with either insufficient renal function or undocumented serum creatinine. These data demonstrate that osteoporosis could be a disease state that should be more closely analyzed through drug utilization reviews and represent yet another opportunity for improved collaboration between medical directors and consultant pharmacists.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14613601&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Effect of alendronate on bone ingrowth into porous tantalum and carbon fiber interbody devices: an experimental study on spinal fusion in pigs.

Zou X, Xue Q, Li H, Bunger M, Lind M, Bunge C.

Orthopaedic Research Laboratory, Spine Section-Department of Orthopaedics, Aarhus University Hospital, Aarhus, Denmark. zxnong hotmail.com

Recent studies have reported that bisphosphonates reduce the resorption of grafted bone and inhibit bone resorption at a bone-implant interface. However, it is not known whether bisphosphonates affect bone ingrowth into porous biomaterial or spine fusion interbody devices with an autograft. In this study, 18 pigs (9 in each group) underwent anterior intervertebral lumbar arthrodeses at L2-3, L4-5 and L6-7. Each level was randomly allocated to one of the 3 implants: a solid piece of porous tantalum (Hedrocel), a porous tantalum ring or a carbon fiber cage both packed with an autograft. Alendronate was given orally to one of the groups. The radiographic and histological findings in the two groups 3 months after operation were similar in these devices. Histological examination showed that the original graft was entirely replaced by new trabecular bone in both groups. On histomorphometric analysis, the bone volume fraction, both inside the central hole of porous tantalum ring and in the porous tantalum, was larger in the pigs given alendronate than in the controls, but the fraction inside and around the central hole of the carbon fiber cage was not affected by this treatment. Short-term alendronate treatment, in a relatively low dose, does not impair the formation of new bone, but increases bone ingrowth into the central hole of the porous tantalum ring and the pores of the porous tantalum in this porcine model. This may be an effective way to enhance early biologic fixation of porous intervertebral implants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14620983&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Differentiating the mechanisms of antiresorptive action of nitrogen containing bisphosphonates.

van Beek ER, Cohen LH, Leroy IM, Ebetino FH, Lowik CW, Papapoulos SE.

Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. E.R.van_Beek lumc.nl

Bisphosphonates (BPS) inhibit bone resorption and are divided into two classes according to their chemical structure and mechanism of action: nonnitrogen containing BPS such as etidronate and clodronate that are of low potency and inhibit osteoclast function via metabolism into toxic ATP-metabolites and nitrogen-containing BPS (NBPS), such as alendronate and risedronate that inhibit the enzyme of the mevalonate biosynthetic pathway farnesyl pyrophosphate synthase (FPPS), resulting in inhibition of the prenylation of small GTP-binding proteins in osteoclasts and disruption of their cytoskeleton. Previously, studies in various cell types suggested, however, that pamidronate functions by mechanism(s) additional or independent of the mevalonate pathway. To examine if such mechanism(s) are also involved in the action of NBPS on osteoclastic bone resorption, we examined the action of alkyl and heterocyclic NBPS with close structural homology on FPPS/isopentenyl pyrophosphate isomerase (IPPI) activity, on osteoclastic resorption, and on reversibility of this effect with GGOH. As expected, both pamidronate and alendronate suppressed bone resorption and FPPS/IPPI activity, the latter with greater potency than the first. Surprisingly, however, unlike alendronate, the antiresorptive effect of pamidronate was only partially reversible with GGOH, indicating the involvement of mechanism(s) of action additional to that of suppression of FPPS. Comparable results were obtained with the heterocyclic NBP NE-21650, a structural analog of risedronate. Thus, despite an effect on FPPS, the actions on bone resorption of some NBPS may involve mechanisms additional to suppression of FPPS. These findings may lead to identification of additional pathways that are important for bone resorption and may help to differentiate among members of the NBP class which are currently distinguished only according to their potency to inhibit bone resorption.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14623056&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
An investigation of the predictors of bone mineral density and response to therapy with alendronate in osteoporotic men.

Drake WM, Kendler DL, Rosen CJ, Orwoll ES.

Osteoporosis Research Centre, University of British Columbia, Vancouver, British Columbia, V5Z 2K4 Canada. w.m.drake qmul.ac.uk

Male osteoporosis is an important disease, with 25-30% of all hip fractures occurring in men. In a recent randomized, placebo-controlled study of osteoporotic males, alendronate 10 mg daily for 2 yr led to significant increments in bone mineral density (BMD), of a similar magnitude to those observed in postmenopausal women. In this study, specimens collected at intervals during the recent trial of alendronate in male osteoporosis, from 197 of the original 241 participants, were assayed for testosterone, estradiol, IGF-I, IGF binding protein 3 (IGFBP-3), bone-specific alkaline phosphatase [BSAP (serum)], and N-telopeptide of type I collagen corrected for creatinine [NTx (urine)]. Together with fracture and densitometry data from the original study, relationships were examined between BMD and serum IGF-I, IGFBP-3, testosterone, estradiol, BSAP, and urine NTx, both at baseline and during treatment with alendronate, to gain possible insights into the pathogenesis of male osteoporosis. Statistically significant (P <or= 0.05) associations were documented, at baseline, between the presence of vertebral fracture and each of serum IGF-I, serum IGFBP-3, serum free testosterone, total spine BMD, and total body BMD. No statistically significant correlations were observed between any of the baseline variables (IGF-I, IGFBP-3, estradiol, testosterone, and presence of vertebral fracture) and the BMD response to alendronate at any site. In a multivariate analysis, used to identify possible combinations of factors capable of predicting baseline BMD or response to alendronate, statistically significant (P <or= 0.01) relationships were seen, at baseline, between BMD and body mass index, age, and prior fracture. However, no statistically significant relationships were seen between any of the baseline variables (age, body mass index, testosterone, estradiol, IGF-I, IGFBP-3, and prior fracture) and change in BMD at any site. These data suggest that among men with osteoporosis it is not possible to identify patients who would be particularly good candidates for therapy with alendronate on the basis of biochemical or hormonal markers. Alendronate therapy appears to benefit osteoporotic males equally, irrespective of baseline serum testosterone, estradiol, IGF-I, or markers of bone turnover.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14671165&dopt=Abstract alendronate Fosamax



alendronate, Fosamax
Alendronate zwitterions bind to calcium cations arranged in columns.

Fernandez D, Vega D, Goeta A.

Escuela de Ciencia y Tecnologia, Universidad Nacional de General San Martin, Calle 91 3391, 1653 Villa Ballester, Buenos Aires, Argentina. fernande tandar.cnea.gov.ar

Alendronate is used clinically in the treatment of skeletal disorders, the mode of action depending on the adsorption to calcium hydroxyapatite crystals (bone). In the title compound, calcium 4-ammonium-1-hydroxybutylidene-1,1-bisphosphonate, Ca(2+).2C(4)H(12)NO(7)P(2)(-), alendronate is a zwitterion, possessing one negative charge on each PO(3) group and a protonated N atom. The zwitterion is disposed with its negative end facing the Ca(2+) ion, while its positive end is stretched in the opposite direction. The geometry of the carbon chain is all-trans, while the hydroxy group is approximately gauche. The Ca(2+) ion lies on a twofold axis parallel to b. The coordination sphere around the metal cation is octahedral and is determined by monodentate- and bidentate-coordinated alendronate zwitterions. The O.O bite distance is 3.080 (2) A. Coordinated Ca(2+) metal cations are arranged at the centre of a column running along c.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14671354&dopt=Abstract alendronate Fosamax