Fosamax scientific update |
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J Control Release. 2010 Jul 2.
Kim CW, Yun YP, Lee HJ, Hwang YS, Kwon IK, Lee SC.
Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul 130-701, South Korea.
Inhibition of osteoclastogenesis in assembly of aldendronate [In situ fabrication of aldendronate-loaded calcium phosphate microspheres: Controlled release for inhibition of osteoclastogenesis.]
Bioabsorbable calcium phosphate (CaP) microspheres that can incorporate alendronate (ALD) through an in situ loading process and can control the ALD release rate have been described. ALD loading into CaP microspheres could be accomplished by emulsification (water-in-oil) and a subsequent CaP nucleation/growth process within the water droplets, which was initiated by a urea-mediated solution precipitation technique. ALD-loaded microspheres with a mean size range of 163 approximately 210 mum were obtained in a spherical shape. Inductively coupled plasma mass spectroscopy (ICP-MS), spectrophotometric analysis, and thermogravimetric analysis (TGA) showed that the amount of ALD loaded into the microspheres increased when the ALD feed content increased. Energy-dispersive X-ray spectroscopy (EDX) analysis revealed that the in situ loading process enabled the ALD loading throughout the microspheres. X-Ray diffraction (XRD) analysis demonstrated that crystalline hydroxyapatite (HAp) and amorphous CaP phases coexisted within the microspheres. In addition, the increased loading of ALD resulted in a larger proportion of the amorphous CaP phase within the microspheres. The ALD release rate could be controlled depending on the dissolution rate of microspheres, and ALD could be released over a period of 40 days. The evaluation of the biological activity showed that ALD-loaded CaP microspheres directly blocked osteoclast formation by releasing ALD to monocytic precursor cells and effectively inhibiting their differentiation into osteoclasts.
J Stroke Cerebrovasc Dis. 2010 Jul 1.
Sato Y, Iwamoto J, Honda Y.
Department of Neurology, Mitate Hospital, Tagawa, Japan.
Analysis of stroke patients suffering from hip fractures [An Open-Label Trial Comparing Alendronate and Alphacalcidol in Reducing Falls and Hip Fractures in Disabled Stroke Patients.]
Although vitamin D supplementation has been suggested to reduce the risk of falling in ambulatory or institutionalized elderly persons, no study has examined whether it reduces the frequency of falling in immobilized stroke patients who have immobilization-induced hypercalcemia reflecting increased bone resorption leading to inhibited renal synthesis of 1, 25-dihydroxyvitamin D (1, 25-[OH]2D). Bisphosphonate is known to reduce immobilization-induced hypercalcemia by inhibiting bone resorption of calcium. This study compared the efficacy of 2 drugs in reducing the risk of falling in patients with long-standing stroke. Eighty-two elderly patients with poststroke hemiparesis were followed for 1 year. The patients were randomly assigned to one of 2 groups; 41 patients received alendronate 35mg once weekly, and 41 patients received alphacalcidiol 1mug daily. The number of falls per person and incidence of hip fracture in the 2 groups were compared. At baseline, all patients had a low serum 1, 25-[OH]2D level. Alphacalcidol therapy enhanced immobilization-induced hypercalcemia by increasing intestinal calcium absorption, leading to a reduction of serum 1, 25-[OH]2D level, while alendronate therapy enhanced 1, 25-[OH]2D production by decreasing hypercalcemia. Alendronate treatment accounted for a 55% reduction in falls (95% confidence interval [CI]=25-72%; P=.0021). During the 1-year study period, hip fracture occurred in 1 of 41 subjects in the alphacalcidol group and in no subjects in the alendronate group. Bone mineral density was increased by 3.2% in the alendronate group and decreased by 0.1% in the alphacalcidol group (P < .0001). Alendronate therapy increased serum 1, 25-[OH]2D levels by improving immobilization-induced hypercalcemia, which may lead to decreased falling and subsequent hip fractures.
Bull Cancer. 2010 Jul 1. [Epub ahead of print]
Clézardin P.
Inserm, unité U664, Faculté de médecine Lyon-Est (domaine Laennec), 69372 Lyon, France.
Bisphosphonate zoledronate shows anti tumour properties [Antitumor properties of the bisphosphonate zoledronate and potential therapeutic implications in the clinic.] [Article in French]
Zoledronate, just as other bisphosphonates, inhibit osteoclast mediated bone resorption. This is the reason why they are used in the treatment of bone metastasis, in order to block osteolysis. Zoledronate and some other bisphosphonates (clodronate, pamidronate, ibandronate, alendronate, risédronate, minodronate) also exhibit antitumor properties in vitro. They act directly on tumor cells by blocking tumor cell adhesion, invasion and proliferation, and by inducing tumor cell apoptosis. However, their high bone mineral affinity decreases their bioavailability to a significant extent and, thus, should weaken their in vivo antitumor potential. Despite of this, several studies (most of them being performed with zoledronate) show that bisphosphonates have an in vivo antitumor activity. This review focuses on zoledronate and on results obtained in several experimental models showing that this bisphosphonate interferes with the growth of tumors and metastases which are thriving in tissues others than the skeletal tissue. The significance of these findings is discussed in the light of several ongoing clinical trials which examine the benefits of using zoledronate and other bisphosphonates in the adjuvant treatment of cancers at an early stage of the disease.
Bone. 2010 May 15. [Epub ahead of print]
Sloan AV, Martin JR, Li S, Li J.
Department of Biology, School of Science, Indiana University Purdue University Indianapolis, 723 West Michigan Street, SL306, Indianapolis, IN 46202 USA.
Stress fracture reveals opposite effects through parathyroid hormone and bisphosphonate [Parathyroid Hormone and Bisphosphonate Have Opposite Effects on Stress Fracture Repair.]
This study was aimed to investigate the effects of Parathyroid hormone (PTH) and alendronate (ALN) on stress fracture repair. Stress fractures were induced in the ulnae of female adult rats. Animals were treated daily with vehicle, PTH (40microg/kg) or alendronate (2microg/kg), respectively. Bone mineral content (BMC) and bone mineral density (BMD) of bilateral ulnae were measured at two, four and eight weeks following induction of stress fracture. Histology at the ulna midshaft was undertaken at 2 and 4weeks and mechanical testing was done at 8weeks after stress fracture. PTH increased BMC significantly by 7% at 4weeks and BMD and BMC significantly by 10% and 7% at 8weeks compared to the control. Alendronate did not change BMD or BMC in comparison with the control. PTH significantly stimulated bone formation by 114% at 2weeks, increased intracortical resorption area by 23% at 4weeks, and enhanced the ultimate force of the affected ulnae by 15% at 8weeks compared to the control. Alendronate significantly suppressed bone formation rate by 77% compared to the control at 4weeks. These data indicate that PTH may accelerate intracortical bone remodeling induced by microdamage and alendronate may delay intracortical bone remodeling during stress fracture repair in rats. This study suggests that PTH may be used to facilitate stress fracture repair whereas bisphosphonates may delay tissue level repair of stress fractures.
Int J Rheum Dis. 2009 Jul;12(2):149-54.
Lee JK.
J. K. Lee Orthopedic and Traumatology, Petaling Jaya, Selangor, Malaysia. osteoporosis_jklee@yahoo.com
Patients show typical femoral disphyseal fractures when treated by alendronate sodium [Bilateral atypical femoral diaphyseal fractures in a patient treated with alendronate sodium.]
Antiresorptive agents have been used as primary or first-line therapy in managing patients with osteoporosis. Bisphosphonates in particular are used widely to reduce bone resorption, increase bone mineral density, improve bone quality and therefore reduce fracture risk. However, prolonged use of bisphosphonates may cause over-suppression of bone resorption, leading on to accumulation of micro-damage in bone. This in turn might lead on to atypical femoral fractures. A patient treated with alendronate sodium for 8 years, and presenting with bilateral atypical femoral diaphyseal fractures is reported. X-rays of both femurs showed typical horizontal fracture line involving the thick lateral cortex with short oblique fracture pattern over the medial cortex. This fracture pattern was further confirmed with intra-operative examination of the fracture ends. Histopathological examination of the endocortical fragment removed from the proximal fracture end showed absence of osteoclasts and osteoblasts. Bone mineral density with dual energy X-ray absorptiometry (DXA) scan showed osteopenia over the femoral neck. Blood investigations did not show significant abnormalities. Bone turnover marker levels were not reliable, as presence of fracture might have altered the marker levels. Both femoral fractures united well. The patient reported here had complete pictures on X-ray examination, intra-operative findings, histopathological examination, DXA, as well as blood test results. Complete data should be collected from patients treated with alendronate sodium presenting with atypical femoral fractures to show any link between the use of alendronate sodium with atypical fracture of femur.
ACS Appl Mater Interfaces. 2009 Feb;1(2):266-9.
Jiang K, Fan D, Belabassi Y, Akkaraju G, Montchamp JL, Coffer JL.
Effect of silicon nanowires on calcification and cell proliferation [Medicinal surface modification of silicon nanowires: impact on calcification and stromal cell proliferation.]
Medicinal surface modification of silicon nanowires (SiNWs) with selected bisphosphonates, such as the known antiosteoporotic drug alendronate, is described. In terms of specific assays relevant to orthopedic applications, the impact of selected bisphosphonate attachment on acellular calcification in simulated plasma is reported. To further investigate biocompatibility, proliferation assays of these modified nanowires were carried out using an orthopedically relevant cell line: mesenchymal stem cells derived from mouse stroma. It is found that the identity of the bisphosphonate ligand strongly and sensitively impacts its resultant cytotoxicity.
Int J Rheumatol. 2009;2009:253432. Epub 2010 Jan 27.
Somford MP, Geurts GF, den Teuling JW, Thomassen BJ, Draijer WF.
Department of Orthopaedic Surgery, Academic Medical Center, Postbus 22660, 1100 DD Amsterdam, The Netherlands.
Long term effect of alendronate [Long-Term Alendronate Use Not without Consequences?]
A previously unknown side effect of biphosphonate use is emerging. In a specific patient group on long term biphosphonate therapy stress femur fractures seem to occur. The typical presentation consists of prodromal pain in the affected leg and/or a discrete cortical thickening on the lateral side of the femur in conventional radiological examination or the presentation with a spontaneous transverse subtrochanteric femur with typical features. We present three cases of this stress fracture in patients on bisphosphonate therapy. One of these patients suffered a bilateral femur fracture of the same type. In our opinion, in patients on bisphosphonate therapy who present with a spontaneous femur fracture, seizing therapy is advisable. In bilateral cases preventive nailing should be considered.
Pediatr Endocrinol Rev. 2008 Oct;6 Suppl 1:144-8.
Skordis N, Ioannou YS, Kyriakou A, Savva SC, Efstathiou E, Savvides I, Christou S.
Paediatric Endocrine Unit, Department of Paediatrics, Makarios Hospital, Nicosia, Cyprus. nskordis@cytanet.com.cy
Impact of biosphosphonate on patients with major thalassaemia [Effect of bisphosphonate treatment on bone mineral density in patients with thalassaemia major.]
BACKGROUND: Bisphosphonates are potent inhibitors of osteoclastic bone resorption and have been recently used in thalassaemia major (TM) osteoporosis with encouraging results. OBJECTIVE: The aim of the study is to investigate the effect of two Bisphosphonate drugs, Alendronate and Pamidronate on bone mass in patients of both genders with TM, treated in our Center. SUBJECTS AND METHODS: 53 (22 males, 31 females) Thalassaemic patients of Greek Cypriot origin were randomly divided into two groups. 29 patients in group A with a mean age of 33, 32 years were treated with alendronate and 24 patients in group B with a mean age of 34, 36 years received pamidronate for a period of 2 years. The effectiveness of both drugs was estimated based on the change of Bone mineral density (BMD) values of lumbar spine and femoral neck. Bone mineral density (BMD) of lumbar spine and femoral neck was measured by dual-energy X-ray absiorptiometry. All patients were on the standard treatment protocol of Thalassaemia. Statistical analysis was performed with the SPSS program. RESULTS: After completion of treatment with pamidronate the mean lumbar spine BMD has improved from -2.813 to -2.174 (p<0.001) and the mean hip BMD from -2.138 to -2.078 (p=0.018). The change of spine BMD in patients who received alendronate was from -2.720 to -2.602 (p=0.059) and the changes in BMD at the femoral neck from -2.035 to -2.007 (p=0.829). CONCLUSIONS: This study demonstrates the efficacy of two bisphosphonate drugs in improving BMD values in patients with TM and osteoporosis. Since the origin of bone disease in TM is multifactorial and some of the underlying pathogenic mechanisms are still unclear, further research in this field is needed, which will allow the design of optimal therapeutic measures.
Pediatr Endocrinol Rev. 2008 Oct;6 Suppl 1:86-93.
Voskaridou E, Terpos E.
Thalassaemia Center, Laikon General Hospital, Athens, Greece. ersi_voskaridou@yahoo.com
Analysis of osteoporosis in thalassemia [Pathogenesis and management of osteoporosis in thalassemia.]
Osteopenia and osteoporosis cause severe problems in thalassemic patients. The pathogenesis of bone loss in thalassemia is multifactorial. The delay in sexual maturation, the presence of diabetes and hypothyroidism, the parathyroid gland dysfunction, the accelerated hemopoiesis with progressive marrow expansion, the direct iron toxicity on osteoblasts, the iron chelators, the deficiency of growth hormone or insulin growth factors, all have been identified as major causes of osteoporosis in thalassemia. However, despite the normalization of hemoglobin levels, adequate hormone replacement and effective iron chelation, patients continue to show an unbalanced bone turnover with an increased resorptive phase resulting in seriously diminished bone mineral density (BMD). During the last decade bisphosphonates have been used for the management of osteoporosis in thalassemia. Alendronate, pamidronate and zoledronic acid have shown efficacy in increasing BMD in thalassemic patients. However, further trials must be conducted in order to clarify the exact role of each bisphosphonate, the long-term benefit and side-effects as well as the effects of the combination of bisphosphonates with other effective agents, such as hormonal replacement, on thalassemia osteoporosis.
Chin J Physiol. 2008 Dec 31;51(6):331-7.
Iwamoto J, Matsumoto H, Takeda T, Sato Y, Xu E, Yeh JK.
Department of Sports Medicine, Keio University School of Medicine 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. jiwamoto@sonata.plala.or.jp
Impact of alendronate on bone mass [Effects of alendronate and alfacalcidol on the femoral bone mass and bone strength in orchidectomized rats.]
The purpose of the present study was to compare the effects of alendronate (ALN) and alfacalcidol (ALF) on the femoral bone mass and bone strength in orchidectomized rats and to clarify the skeletal benefits of combined administration of ALN and ALF. Fifty male Sprague-Dawley rats, 3 months of age, were randomized by the stratified weight method into five groups: the age-matched control (CON), orchidectomy (ORX), ORX + ALN (2.5 microg/kg, s.c., 5 times a week), ORX + ALF (0.1 microg/kg, p.o., 5 times a week), and ORX + ALN + ALF groups. After 12 weeks of feeding, the femoral distal metaphysis and mid-diaphysis were processed for peripheral quantitative tomographic analysis and biomechanical testing. In the femoral distal metaphysis, ALN prevented the ORX-induced reduction in the trabecular volumetric bone mineral density (vBMD) and breaking energy, and ALF prevented the ORX-induced reduction in the trabecular vBMD and increased the breaking energy to values above those observed in the CON group. Both ALN and ALF increased the maximum load to values above those observed in the ORX group. The improvements in parameters described above were more pronounced when ALN and ALF were administered in combination. In the femoral mid-diaphysis, on the other hand, ALN did not significantly affect the cortical bone parameters, whereas ALF increased the cortical area and maximum load to values above those observed in the ORX group. Furthermore, no apparent benefit of combined administration of ALN and ALF was observed. These findings suggest differential effects of ALN and ALF on femoral bone mass and the beneficial effects of combined administration of ALN and ALF on the trabecular bone of the femur in ORX rats.
HSS J. 2007 Sep;3(2):169-72. Epub 2007 Mar 31.
Issack PS, Lauerman MH, Helfet DL, Doty SB, Lane JM.
Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
Information of alendronate inducing bone morphogenetic protein [Alendronate inhibits PTH (1-34)-induced bone morphogenetic protein expression in MC3T3-E1 preosteoblastic cells.]
The bisphosphonate class of antiresorptive drugs and active forms of parathyroid hormone (PTH (1-34)) have been used clinically to enhance bone mass and density in patients with osteoporosis. Abundant evidence suggests that the mechanism by which PTH (1-34) increases bone density is stimulation of osteoblast differentiation. Although bisphosphonates have been classically thought to increase bone density by inhibiting osteoclasts, there is increasing evidence to suggest that bisphosphonates have direct stimulatory effects on osteoblast differentiation. Interestingly, in patients with osteoporosis, combination therapy with bisphosphonates and PTH (1-34) is not synergistic in increasing bone density; bisphosphonates appear to blunt the effect of PTH (1-34). To begin to understand the mechanism governing the effects of these agents on osteoblasts and a possible explanation for their apparent antagonism, we examined the expression of several bone morphogenetic proteins (BMPs) in MC3T3-E1 preosteoblastic cells either untreated, or treated with alendronate, parathyroid hormone, or a combination of the two agents. We find by reverse transcriptase-polymerase chain reaction (RT-PCR) that while alendronate fails to induce the expression of any of the BMPs tested, several BMPs are induced by PTH (1-34). The induction of the PTH (1-34)-inducible BMPs is blocked with simultaneous alendronate treatment. These data suggest that alendronate interferes with PTH (1-34)-induced BMP gene transcription and provides a possible basis for the antagonism observed between the two agents in increasing bone density.
Ginecol Obstet Mex. 2007 Nov;75(11):655-60.
Carranza Lira S.
UMAE, Hospital de Ginecoobstetricia Luis Castelazo Ayala, IMSS, DF Mexico. scarranzal@mexis.com
Relation of bisfosfonates and osteonechrosis [Mandible osteonechrosis associated to bisfosfonates] [Article in Spanish]
INTRODUCTION: Mandibular osteonecrosis (MONC) is an entity associated with the use of powerful bisphosphonates with a prevalence of 1-10% in cancer patients OBJECTIVE: To carry out a literature review with regard MONC, to establish the actual estate of this entity. METHODS: A review of the literature up to September 18, 2007 was done via MEDLINE of the published articles on the topic. They following words were crossed: bisphosphonates, alendronate, clodronic acid, etidronate, ibandronate, risedronate, osteonecrosis, jaw. Atotal of 114 references were obtained and the best were chosen. RESULTS: MONC presents in several ways: massive gingival edema without or with of necrotic bone exhibition in oral cavity accompanied by intense pain or asymptomatic. Symptoms can simulate common dental problems such as caries or periodontal illness. MONC can presents spontaneously or after a dental extraction. Several theories have been mentioned but at this moment any of them is completely satisfactory. The diagnosis is carried out mainly with based in history: age (7th life decade of), intravenous bisphosphonates use, long-term use of them, cancer, dental extraction and chemotherapy use. The treatment can be variable. CONCLUSION: High power and long duration bisphosphonates are associated with a greater risk of MONC, although a narrow surveillance should be maintained in those used for osteoporosis treatment.
Reumatizam. 2007;54(2):89-92.
Grazio S, Morović-Vergles J.
Klinika za reumatologiju, fizikalnu medicinu i rehabilitaciju, Klinicka bolnica "Sestre milosrdnice", Vinogradska 29, 10000 Zagreb.
Alendronate and Vitamin D usefullness [Alendronate and vitamin D (Fosavance): persistence, adherence and importance of vitamin D] [Article in Croatian]
Persistence and adherence are major determinants of optimal results in the treatment of osteoporosis. In order to improve the efficacy of antiresorptive drugs, fewer demands on patients and better adherence were obtained with less frequent dosing schedule. Once-weekly and once-monthly oral bisphophonates showed equivalency with once daily medications. Comparison of persistence and adherence between weekly and monthly bisphosphonate regimens revealed conflicting results. In Croatia, persistence and adherence of weekly alendronate seem to be better than in other countries. In the light of compliance problems there is a need to assure adequate intake of vitamin D, because it is essential for prevention and treatment of osteoporosis and osteoporotic fractures. Vitamin D has other beneficial effects, particularly on neuromuscular performances. A high prevalence of vitamin D inadequacy was seen across all geographic regions. Weekly alendronate and vitamin D in one tablet provides proven fracture prevention at the spine and hip, and assure that patients receive a weekly dose of vitamin D.
Biomaterials. 2007 Apr 20;
von Knoch F, Eckhardt C, Alabre CI, Schneider E, Rubash HE, Shanbhag AS.
Massachusetts General Hospital & Harvard Medical School, Boston, MA, USA.
Anabolic effects of bisphosphonates on peri-implant bone stock.
The present study suggest that bisphosphonates may more than compensate for the well-documented negative effects of wear debris on peri-implant bone stock. The combined antiresorptive and osteoanabolic effects of bisphosphonates on periprosthetic bone stock may have an important role for critically improving the biological fixation and ultimate durability of total joint arthroplasty.
The long-term durability of total joint replacements is critically dependent on adequate peri-implant bone stock, which can be compromised by wear
debris-mediated osteolysis. This study investigated the effects of bisphosphonates on enhancing peri-implant bone in the presence of clinically relevant
ultra-high molecular weight polyethylene (UHMWPE) wear debris. Fiber-mesh coated titanium-alloy plugs were implanted bilaterally in the femoral condyles of
36 New Zealand white rabbits. Implants in the left femora were covered with submicron UHMWPE particles during surgery. Rabbits were administered either no
drug, subcutaneous alendronate weekly (1.0mg/kg/week) or a single dose of intravenous zoledronate (0.015mg/kg). A total of 6/12 rabbits in each group were
sacrificed at 6 weeks and the remainder at 12 weeks postoperatively. Peri-implant bone stock was analyzed radiographically and histomorphometrically.
Radiographically, both bisphosphonates significantly increased periprosthetic cortical thickness at 6 weeks (p<0.0001; alendronate: +18%; zoledronate: +11%)
and at 12 weeks (p=0.001; alendronate: +17%; zoledronate:+19%). Histomorphometrically, alendronate and zoledronate raised peri-implant bone volume (BV/TV) up
to 2-fold after 6 weeks without added wear debris and more than 3-fold when wear debris was present. Furthermore a 6-week bisphosphonate treatment increased
osteoid thickness in the absence of wear debris (alendronate: +132%, p=0.007; zoledronate: +67%, p=0.51) and in the presence of wear debris (alendronate:
+134%, p=0.023; zoledronate: +138%, p=0.016). In summary, alendronate and zoledronate treatment increased periprosthetic bone stock in a rabbit femoral
model, particularly in the presence of UHMWPE wear debris. These new findings suggest that bisphosphonates may more than compensate for the well-documented
negative effects of wear debris on peri-implant bone stock. The combined antiresorptive and osteoanabolic effects of bisphosphonates on periprosthetic bone
stock may have an important role for critically improving the biological fixation and ultimate durability of total joint arthroplasty.
Ir Med J. 2007 Mar;100(3):410-1.
Khosa AD, Nayyar MS, Beirne JC.
Maxillofacial Unit, St James Hospital, Dublin.
Osteochemonecrosis of jaws and bisphosphonates.
Zoldronic acid (bisphosphonate), which is more effective than Pamidronate in controlling hypercalcaemia of bone and reducing the skeletal related events in patients with metastatic breast cancer, multiple myeloma, hypercalcaemia of malignancy, paget's disease and bone metastasis from prostate and lung cancer.
Osteochemonecrosis of the jaws is a well described side effect of bisphosphonate therapy. Bisphosphonates are non metabolised analogues of pyrophosphate that
are capable of localizing to bone, slowing both rate of growth and rate of dissolution therefore reducing the rate of bone turnover. Although the exact
mechanism is not clear but it has been established that bisphosphonates target osteoclast, inhibiting their function in several ways: There are two types of
bisphosphonates. The first are oral preparations of bisphosphonates, which include Alendronate and Risedronate. They are indicated for the treatment of
osteoporosis. They are considered as lower risk of osteochemonecrosis. The second are administered intravenously. Pamindronate is a first generation
bisphosphonate; 90 mg administered intravenouly over 2-24 hours every 3-4 weeks. The next generation of intravenous bisphosphonate is Zoldronic acid, which
is more effective than Pamidronate in controlling hypercalcaemia of bone and reducing the skeletal related events in patients with metastatic breast cancer,
multiple myeloma, hypercalcaemia of malignancy, paget's disease and bone metastasis from prostate and lung cancer.
Ren Fail. 2007 May;29(4):471-476.
Yanik B, Bavbek N, Yanik T, Inegol I, Kanbay M, Turgut FH, Uz E, Akcay A.
School of Medicine, Physical Medicine and Rehabilitation, Fatih University. Ankara. Turkey.
The Effect of Alendronate, Risedronate, and Raloxifene on Renal Functions, Based on the Cockcroft and Gault Method, in Postmenopausal Women.
The present study aimed to assess the risk of renal toxicity associated with oral alendronate, risedronate, and raloxifene in the treatment of osteoporosis, prospectively. The study results demonstrated that alendronate, risedronate, and raloxifene are all safe drugs for renal functions in the treatment of osteoporosis.
Background. Oral alendronate, risedronate, and raloxifene are effective treatment options in the management of postmenopausal osteoporosis. There is little
previously reported about the renal safety profiles of these three agents in osteoporosis. We aimed to assess the risk of renal toxicity associated with oral
alendronate, risedronate, and raloxifene in the treatment of osteoporosis, prospectively. Methods. One hundred and twenty-seven patients with osteoporosis
and osteopenia according to lumbar or femoral-neck bone mineral density t score were enrolled in the study. The patients were randomized to alendronate 70 mg
once weekly (n = 47), risedronate 35 mg once weekly (n = 44), or raloxifene 60 mg per day (n = 36) for one year. Preliminary screening included medical
history, physical examination, lumbar and femoral bone mineral densitometry measurement, and blood biochemical tests, including renal function tests. The
biochemical markers were then assessed at the end of 12 months. Results. There was no significant difference between basal and final renal function
parameters of each group. Also these parameters did not differ between the three groups after 12 months of treatment period. Conclusions. These results
demonstrate that alendronate, risedronate, and raloxifene are all safe drugs for renal functions in the treatment of osteoporosis.
J Bone Miner Res. 2006 Oct;21(10):1565-70.
Adami S, Isaia G, Luisetto G, Minisola S, Sinigaglia L, Gentilella R, Agnusdei D, Iori
ICARO Study Group
Fracture Incidence and Characterization in Patients on Osteoporosis Treatment: The ICARO
The present study aimed to analyze, in postmenopausal women with established osteoporosis, defined as the occurrence of new vertebral or nonvertebral fragility fractures in patients prescribed, for at least 1 year, alendronate, risedronate, or raloxifene, with a compliance >50%. The study reported that inadequate compliance to treatment and lack of supplementation of calcium and vitamin D are major determinants of this poor response.
None of the available osteoporosis therapies have been shown to completely abolish the risk of
fractures. In clinical practice, the outcome may be even poorer. In 880 patients prescribed
with antiresorptives (alendronate, risedronate, and raloxifene) for >1 year, a fragility
fracture was recorded in 8.9%/year of them. This incidence is considerably higher than that
observed in randomized clinical trials, and it was significantly related to poor compliance
and lack of supplementation with calcium and vitamin D. Introduction: Osteoporotic fracture is
one of the most important public health concerns among the elderly. Currently available
therapies have been shown to significantly decrease the risk of fracture, although none of
them completely abolishes this risk. In clinical practice, poor treatment response may also
result from a number of other factors. Materials and Methods: The Incidence and
ChAracterization of inadequate clinical Responders in Osteoporosis (ICARO) is a multicenter,
observational study carried out in Italy. It aimed to analyze, in postmenopausal women with
established osteoporosis, the risk factors for an "inadequate clinical response" to drug
therapy, defined as the occurrence of new vertebral or nonvertebral fragility fractures in
patients prescribed, for at least 1 year, alendronate, risedronate, or raloxifene, with a
compliance >50%. Results: In 880 patients treated with antiresorptive agents for a median of
2.0 years (95% CI: 1.0-4.5) years, the "inadequate clinical responder (ICR)" subjects over the
observation period were 220 (25%), with an annual incidence of 8.9%. ICRs, compared with
"adequate clinical responders (ACRs)," had more pretreatment fractures and were treated longer
(2.8 versus 1.8 years; p < 0.001). After multiple adjustment for these confounding factors,
significant determinants of inadequate clinical response were a poorer treatment compliance
and a less frequent co-administration of calcium and vitamin D supplements. Conclusions: The
incidence of fractures during treatment with antiresorptive agents in a clinical setting is
considerably higher than that observed in randomized clinical trials. Inadequate compliance to
treatment and lack of supplementation of calcium and vitamin D are major determinants of this
poor response.
Endocr Regul. 2003 Dec;37(4):225-38.
Stepan JJ, Alenfeld F, Boivin G, Feyen JH, Lakatos P.
3rd Clinic of International Medicine, Charles University School of Medicine, Prague, Czech Republic.
Mechanisms of action of antiresorptive therapies of postmenopausal osteoporosis.
The process of bone remodeling plays a role in plasma calcium homeostasis and serves to modify bone architecture in order to meet changing mechanical needs, to maintain osteocyte viability, and to repair microdamage in bone matrix. The study suggest that estrogens and raloxifene suppress bone remodeling to the premenopausal range, maintaining the function of osteoblasts and osteocytes.
In the treatment of osteoporosis, the aim of the antiresorptive therapy is to restore bone density by decreasing bone remodeling. The process of bone remodeling plays a role in plasma calcium homeostasis and serves to modify bone architecture in order to meet changing mechanical needs, to maintain osteocyte viability, and to repair microdamage in bone matrix. Estrogen deficiency results in a number of detrimental effects on bone, including suppression of osteocyte survival as well as impairment of osteoblast response to mechanical stimuli and repair of ageing bone. In this review, effects of available antiresorptive therapies on endocrine regulations of bone metabolism in postmenopausal osteoporosis are compared. The aim of antiresorptive treatment is to ensure adequate bone remodeling, reparation of microdamage of bone, and increased bone strength. Ideally, this effect should be maintained long-term. Several agents are approved for the treatment of osteoporosis. Calcitonin transiently inhibits osteoclast activity without decreasing osteoblast collagen synthesis. Aminobisphosphonates decrease bone remodeling by decreasing osteoclast activity and by inducing osteoclast apoptosis. This allows more time for secondary mineralization to proceed to completion in the existing bone tissue mass, so increasing the mechanical resistance of bone to loading. Estrogens and raloxifene (a selective estrogen receptor modulator that acts as an estrogen agonist in bone) suppress bone remodeling to the premenopausal range, maintaining the function of osteoblasts and osteocytes. In the placebo-controlled osteoporosis treatment trials, all the above treatments reduced the risk of fractures. Raloxifene therapy was also associated with a favorable or neutral effect in the cardiovascular system, and a reduced incidence of breast cancer. Selection of appropriate drug for treatment of postmenopausal osteoporosis should take into account the long-term effect of the antiresorptive agent on bone. Moreover, the effects on other tissues ++should also be considered, and this encompasses both safety concerns, as well as the potentially beneficial effects on other tissues. Further investigation is needed to evaluate the different modes of action of these agents, and their long-term effects on bone and other tissues.
Obstet Gynecol Surv. 2004 Jun;59(6):446-55; quiz 485.
Kessel B.
Department of Obstetrics, Gynecology and Women's Health, University of Hawaii, John A. Burns School of Medicine, and The Queen's Medical Center, Honolulu, Hawaii 96813, USA.
Hip fracture prevention in postmenopausal women.
The present article make the people able to list the demographic risk factors for osteoporosis and related fractures, to outline the cost and consequences of hip fractures, and to summarize the various pharmacologic and non-pharmacologic interventions used to reduce the risk of hip fracture.
Hip fracture is a devastating outcome associated with postmenopausal osteoporosis. This fracture causes considerable pain, disability, diminished quality of life, and mortality. Although bone loss is an important factor associated with hip fracture, there are other demographic and clinical factors such as those that increase the risk of falling (e.g., unsteady gait, medications) that contribute to the likelihood of experiencing a hip fracture. Nonpharmacological interventions to reduce hip fracture risk include regular weight-bearing exercise, fall intervention programs, and external hip protectors. Patients should receive calcium and/or vitamin D supplementation as necessary. Among available pharmacologic options, the bisphosphonates, risedronate (Actonel) and alendronate (Fosamax), have reduced the risk of hip fracture in postmenopausal women with osteoporosis. Raloxifene (Evista), salmon calcitonin nasal spray (Miacalcin), and teriparatide (Forteo) have not demonstrated hip fracture risk reduction in controlled clinical trials. Hormone therapy (HT) reduced hip fracture risk in a recent large placebo-controlled trial; however, the risk/benefit profile of HT has resulted in recommendations to consider alternatives for the management of osteoporosis. Postmenopausal women with osteoporosis should receive adequate calcium/vitamin D supplementation, be encouraged to exercise, and institute risk factor interventions. Treatment with a bisphosphonate should be considered for those who are also at increased risk for hip fracture. TARGET AUDIENCE: Obstetricians & Gynecologyists, Family Physicians LEARNING OBJECTIVES: After completion of this article the reader should be able to list the demographic risk factors for osteoporosis and related fractures, to outline the cost and consequences of hip fractures, and to summarize the various pharmacologic and non-pharmacologic interventions used to reduce the risk of hip fracture.
J Periodontol. 2004 Dec;75(12):1579-85.
Rocha ML, Malacara JM, Sanchez-Marin FJ, Vazquez de la Torre CJ, Fajardo ME.
Institute of Medical Research, University of Guanajuato, Leon, Mexico.
Effect of alendronate on periodontal disease in postmenopausal women: a randomized placebo-controlled trial.
The present study evaluated the effect of 6 months of alendronate (ALN) treatment in 40 postmenopausal women, 55 to 65 years old with established periodontal disease. And the study concluded that ALN treatment improved periodontal disease and bone turnover in postmenopausal women.
BACKGROUND: We investigated the effect of oral alendronate (ALN) treatment on radiological and clinical measurements of periodontal disease in postmenopausal women without hormone replacement therapy. METHODS: We evaluated the effect of 6 months of ALN treatment in 40 postmenopausal women, 55 to 65 years old with established periodontal disease, in a controlled, double-masked, prospective study. Volunteers were paired by age and randomized to receive ALN (10 mg/day) or placebo for the study period. Periodontal mechanical treatment was carried out in both groups. At baseline and after treatment, clinical evaluation, hormone blood levels, distance from the crestal alveolar bone (CAB) to the cemento-enamel junction (CEJ), calcaneus bone mineral density (BMD), hormone levels, serum N-telopeptide (NTx), and bone-specific alkaline phosphatase (BSAP) were assessed. RESULTS: Periodontal disease conditions improved in both groups, but greater improvement in probing depth (-0.8 +/- 0.3 mm versus -0.4 +/- 0.4 mm, P = 0.02) and gingival bleeding (-0.3% +/- 0.13% versus -0.2% +/- 0.06%, P = 0.006) was found in the ALN treated group. Calcaneus BMD increased in the ALN treated group (68 +/- 47 mm3 versus -26 +/- 81 mm3, P = 0.0006). CAB-CEJ distance diminished in the ALN group (-0.4 +/- 0.40 mm versus 0.60 +/- 0.53 mm, P = 0.00008). Marginal reduction in both NTx and BSAP levels was found in the ALN group (-9.4 +/- 6.6 nmol versus -4.3 +/- 4.7 nmol bone collagen equivalents, P = 0.08, and -7.7 +/- 8.4 versus -1.5 +/- 5.0 U/l, P = 0.1, respectively). Hormone levels were unchanged after treatment. Similar improvement of calcaneus BMD and CAB-CEJ distance with ALN treatment was found in obese and non-obese women. CONCLUSION: ALN treatment improved periodontal disease and bone turnover in postmenopausal women.
A systematic review of the effect of alendronate on bone mineral density in men.
In the study the scientists conducted a systematic review of randomized controlled trials to determine whether oral alendronate improves BMD at the lumbar spine and hip in men with low bone mass or prevalent fractures. The study concluded that 10 mg of oral daily alendronate is significantly associated with increase in BMD at the lumbar spine and hip in men over 2-3 yr and that these changes are similar to those previously observed in postmenopausal women.
Alendronate is known to increase bone mineral density (BMD) at the lumbar spine and hip in women, but less information is available in men. We conducted a systematic review of randomized controlled trials to determine whether oral alendronate improves BMD at the lumbar spine and hip in men with low bone mass or prevalent fractures, compared with men treated with placebo, calcium, or vitamin D. In three trials in men, BMD (measured by dual-energy X-ray absorptiometry) increased at 2-3 yr (compared to baseline) at the lumbar spine and femoral neck in alendronate-treated patients compared to controls. The pooled estimates of changes in BMD with 10 mg of alendronate daily compared to controls were as follows: 7.8% over 2-3 yr (95% confidence interval [CI] = 4.8- 10.8) at the lumbar spine and 3.8% (95% CI = 2.3-5.3) at the femoral neck (p < 0.001 for treatment effect in each analysis). Statistically significant heterogeneity of treatment effect was noted between trials. We conclude that 10 mg of oral daily alendronate is significantly associated with increase in BMD at the lumbar spine and hip in men over 2-3 yr and that these changes are similar to those previously observed in postmenopausal women.
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Drug category:Bone resorption inhibitor
 Fosamax scientific update
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