RESUMO
This combined retrospective and prospective study aimed to investigate the relationship between scoliosis, spinal bone mineral density (BMD), and truncal muscle strength in patients with familial dysautonomia (FD). A total of 79 FD patients (40 male, 39 female) aged 5-44 years were included. The severity of scoliosis, lumbar spine BMD (Z-score), and truncal muscle strength were assessed. Correlations were analyzed using Pearson's correlation coefficient. Inverse correlations were observed between scoliosis severity and BMD (r = - 0.328, p = 0.001), as indicated by increasingly negative Z-score values with worsening osteoporosis. There were also inverse correlations between scoliosis and truncal muscle strength (r = - 0.595, p < 0.001). The correlation between scoliosis and age was notable up to 22 years (r = 0.421, p = 0.01), but not in the older age group (22-44 years). Our study identified inverse correlations between osteoporosis and scoliosis, as well as between scoliosis and truncal muscle strength, in FD patients. These findings suggest that there may be a relationship between bone density, muscle strength, and the severity of spinal curvature in this population. While our results highlight the potential importance of early diagnosis and management of osteoporosis, and possibly the benefits of physical therapy to strengthen truncal muscles, further research is needed to determine the direct impact of these interventions on preventing the progression of scoliosis and its associated complications in FD patients. A long-term longitudinal study could provide more insights into these relationships and inform treatment strategies for FD patients.
Assuntos
Disautonomia Familiar , Osteoporose , Escoliose , Humanos , Masculino , Feminino , Idoso , Densidade Óssea/fisiologia , Disautonomia Familiar/complicações , Estudos Retrospectivos , Estudos Prospectivos , Estudos Longitudinais , Osteoporose/complicações , Vértebras Lombares , Força Muscular , Absorciometria de Fóton/métodosRESUMO
Postmenopausal osteoporosis is mainly caused by increased bone remodeling resulting from estrogen deficiency. Indications for treatment are based on low areal bone mineral density (aBMD, T-score ≤ -2.5), typical fragility fractures (spine or hip), and more recently, an elevated 10-year fracture probability (by FRAX®). In contrast, there is no clear definition of osteoporosis nor intervention thresholds in younger individuals. Low aBMD in a young adult may reflect a physiologically low peak bone mass, such as in lean but otherwise healthy persons, whereas fractures commonly occur with high-impact trauma, i.e., without bone fragility. Furthermore, low aBMD associated with vitamin D deficiency may be highly prevalent in some regions of the world. Nevertheless, true osteoporosis in the young can occur, which we define as a T-score below -2.5 at spine or hip in association with a chronic disease known to affect bone metabolism. In the absence of secondary causes, the presence of fragility fractures, such as in vertebrae, may point towards genetic or idiopathic osteoporosis. In turn, treatment of the underlying condition may improve bone mass as well. In rare cases, a bone-specific treatment may be indicated, although evidence is scarce for a true benefit on fracture risk. The International Osteoporosis Foundation (IOF) convened a working group to review pathophysiology, diagnosis, and management of osteoporosis in the young, excluding children and adolescents, and provide a screening strategy including laboratory exams for a systematic approach of this condition.
Assuntos
Osteoporose/fisiopatologia , Adolescente , Densidade Óssea/fisiologia , Feminino , Predisposição Genética para Doença , Humanos , Osteoporose/diagnóstico , Osteoporose/etiologia , Osteoporose/terapia , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/etiologia , Gravidez , Complicações na Gravidez/fisiopatologia , Adulto JovemRESUMO
UNLABELLED: The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommend that a marker of bone formation (serum procollagen type I N propeptide, s-PINP) and a marker of bone resorption (serum C-terminal telopeptide of type I collagen, s-CTX) are used as reference analytes for bone turnover markers in clinical studies. INTRODUCTION: Bone turnover markers (BTM) predict fracture risk, and treatment-induced changes in specific markers account for a substantial proportion of fracture risk reduction. The aims of this report were to determine their clinical potential in the prediction of fracture risk and for monitoring the treatment of osteoporosis and to set an appropriate research agenda. METHODS: Evidence from prospective studies was gathered through literature review of the PUBMED database between the years 2000 and 2010 and the systematic review of the Agency for Healthcare Research and Quality up to 2001. RESULTS: High levels of BTMs may predict fracture risk independently from bone mineral density in postmenopausal women. They have been used for this purpose in clinical practice for many years, but there is still a need for stronger evidence on which to base practice. BTMs provide pharmacodynamic information on the response to osteoporosis treatment, and as a result, they are widely used for monitoring treatment in the individual. However, their clinical value for monitoring is limited by inadequate appreciation of the sources of variability, by limited data for comparison of treatments using the same BTM and by inadequate quality control. IOF/IFCC recommend one bone formation marker (s-PINP) and one bone resorption marker (s-CTX) to be used as reference markers and measured by standardised assays in observational and intervention studies in order to compare the performance of alternatives and to enlarge the international experience of the application of markers to clinical medicine. CONCLUSION: BTM hold promise in fracture risk prediction and for monitoring treatment. Uncertainties over their clinical use can be in part resolved by adopting international reference standards.
Assuntos
Biomarcadores/metabolismo , Remodelação Óssea/fisiologia , Osteoporose/metabolismo , Fraturas por Osteoporose/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Densidade Óssea/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/metabolismo , Padrões de Referência , Medição de Risco/métodos , Resultado do TratamentoRESUMO
The aim of this study was to provide confirmation that once-weekly dosing with 70 mg of alendronate (seven times the daily oral dose) and twice-weekly dosing with 35 mg is equivalent to the 10-mg once-daily regimen and to gain more extensive safety experience with this new dosing regimen. Twelve hundred fifty-eight postmenopausal women (aged 42-95 years) with osteoporosis (bone mineral density [BMD] of either lumbar spine or femoral neck at least 2.5 SDs below peak young adult mean or prior vertebral or hip fracture) were assigned to receive oral once-weekly alendronate, 70 mg (n = 519); twice-weekly alendronate, 35 mg (n = 369); or daily alendronate 10 mg (n = 370) for a total of 2 years of double-blind experience. Mean BMD increases from baseline (95% CI) at 24 months in the once-weekly, twice-weekly, and daily treatment groups, respectively, were 6.8% (6.4, 7.3), 7.0% (6.6,7.5), and 7.4% (6.9,7.8) at the lumbar spine and 4.1% (3.8,4.5), 4.3% (3.9,4.7), and 4.3% (3.9,4.7) at the total hip. These increases in BMD as well as the BMD increases at the femoral neck, trochanter, and total body and the reductions of biochemical markers of bone resorption (urinary cross-linked N-telopeptides of type I collagen [NTx]) and bone formation (serum bone-specific alkaline phosphatase [BSAP]) were similar for the three dosing regimens. All treatment regimens were well tolerated with a similar incidence of upper gastrointestinal (GI) adverse experiences. The incidence rates of clinical fractures, captured as adverse experiences, were similar among the groups. The 2-year results confirm the conclusion reached after 1 year that once-weekly alendronate is therapeutically equivalent to daily dosing, providing patients with a more convenient dosing option that may potentially enhance adherence to therapy.
Assuntos
Alendronato/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alendronato/efeitos adversos , Fosfatase Alcalina/sangue , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea , Colágeno/urina , Colágeno Tipo I , Método Duplo-Cego , Esquema de Medicação , Feminino , Fraturas Ósseas/etiologia , Gastroenteropatias/induzido quimicamente , Humanos , Vértebras Lombares/efeitos dos fármacos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Peptídeos/urina , Resultado do TratamentoRESUMO
An ultrasound instrument has recently been developed for the diagnosis and monitoring of osteoporosis (SoundScan 2000, Myriad Ultrasound Systems Ltd., Israel). The instrument measures the speed of propagation of ultrasound waves (SOS, meters per second) along a fixed longitudinal distance of the cortical layer at the tibial shaft. Its in vivo precision is 0.25%. The performance of the SoundScan 2000 was studied in 307 Caucasian women (age range 24-87 years) who also had their bone mineral density (BMD) measured at the spine, femoral neck, and radial shaft by absorptiometric techniques. The SOS ranged from 3471-4226 m/sec (mean 3867). The standardized coefficient of variation (CV), an expression of the effective clinical precision corrected for the spread of measurements (CV/[range/mean]), was 1.6% for the tibial SOS, compared to 1.5%, 3.8%, and 4.4% for spinal, femoral, and radial BMD, respectively. Tibial SOS significantly correlated with age (r = -0.52), time since menopause (r = -0.43), height (r = 0.29), and weight (r = 0.16), as well as with BMD at the radius (r = 0.63), spine (r = 0.50), and femur (r = 0.47). After classification of bone measurements into tertiles, about 60% of the women with low tertile spinal BMD fell within the low tertile of either tibial SOS, femoral BMD, or radial BMD. The results show that measurement of tibial SOS is a precise method of assessing bone status without exposing the patient to sources of radiation.
Assuntos
Densidade Óssea/fisiologia , Osteoporose Pós-Menopausa/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Constituição Corporal , Feminino , Colo do Fêmur/fisiologia , Humanos , Pessoa de Meia-Idade , Rádio (Anatomia)/fisiologia , Reprodutibilidade dos Testes , Coluna Vertebral/fisiologia , UltrassonografiaRESUMO
BACKGROUND: Individuals with Gaucher disease vary significantly with regard to degree of bone disease, but there are no predictive markers for severity of skeletal involvement. AIM: To determine the frequency of polymorphisms of interleukin-6 (IL-6) among patients with Gaucher disease, and the relationship to bone mineral density (BMD) and other markers of disease severity. DESIGN: Case-control study. METHODS: Genotyping for the 174G --> C promoter polymorphism of IL-6 was performed in adult patients with Gaucher disease for whom there was concurrent bone mineral density (BMD) data and in healthy Ashkenazi Jewish controls. RESULTS: The prevalence of allelic variants (58% G/G, 36% G/C, and 6% C/C) was similar in Ashkenazi Jewish adults with Gaucher disease as in Ashkenazi Jewish controls, but significantly different (p < 0.05) from that reported among Caucasians. No statistically significant correlation was found between IL-6 genotypes and BMD or markers of severity of Gaucher disease. Patients with the C/C genotype had relatively mild Gaucher disease. DISCUSSION: The IL-6 polymorphisms appear to be distributed differently in Ashkenazi Jews than among other Caucasians. In Gaucher disease, the C/C genotype may be associated with a milder Gaucher phenotype, and may serve as a mitigating genetic modifier.
Assuntos
Doença de Gaucher/genética , Interleucina-6/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Adolescente , Adulto , Densidade Óssea/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Judeus/genética , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
The purpose of the present study was to evaluate a noninvasive method that utilizes optical processing to analyze the trabecular pattern on bone radiographs. The trabecular network on proximal femur radiographs of 17 intact cadaveric femora was analyzed by optical Fourier transform, yielding a trabecular bone index (TBI) at several locations. The bone mineral density (BMD) of the proximal femur was measured by dual X-ray absorptiometry. Dimensions of the proximal femur were obtained from the radiograph. The bones were fractured in a "fall configuration" to yield the fracture load. A multiple regression model, combining only radiograph- derived parameters-bone dimensions and the TBI at the intertrochanteric region and at the greater trochanter-yielded a correlation of 0.938 with the fracture load. A model combining the BMD at the greater trochanter and at the neck yielded a correlation of 0.928 with the fracture load. When all the variables were introduced into a combined analysis, the correlation with the fracture load was 0.973. The TBI obtained by optical processing of the trabecular bone pattern on femoral radiographs together with bone dimensions derived from these radiographs may serve as an effective estimate for hip fracture risk.
Assuntos
Densidade Óssea , Fêmur/diagnóstico por imagem , Óptica e Fotônica , Absorciometria de Fóton , Adulto , Idoso , Cadáver , Feminino , Fraturas do Quadril/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Medição de RiscoRESUMO
The purpose of this study was to determine whether growth-related changes in bone properties can be detected in prepubertal boys using quantitative ultrasound (QUS) and to determine whether resistance training stimulates bone changes. Two groups, each of thirty 9-10 year-old boys, participated in regular physical education classes or in resistance training. Tibial speed of sound (SOS) (SoundScan 2000, Myriad) was assessed at the beginning of the school year and after 8 months. At baseline, there were no differences between groups in tibial SOS, anthropometric measures or pubertal development. At the end of the year, the tibial SOS increased (p<0.001) in both groups to a similar extent. In addition, there were no differences in the increases in height between the two groups. This indicates that resistance training during the physical education program did not induce changes in bone beyond what would be expected by the mere effect of growing. We conclude that changes in tibial SOS, as obtained with QUS, can be detected in groups of prepubertal boys over a period of 8 months.
Assuntos
Desenvolvimento Ósseo , Tíbia/diagnóstico por imagem , Antropometria , Composição Corporal , Criança , Humanos , Masculino , Músculo Esquelético/fisiologia , Educação Física e Treinamento , Estudos Prospectivos , Valores de Referência , Ultrassonografia , Levantamento de PesoRESUMO
We present a preliminary series of clinical experiments showing that ultrasound modulation of light in tissues allows tissue properties to be determined well inside the tissue. In this series of clinical experiments the optical scattering coefficient determined by the optical technique is compared with the bone density obtained by dual x-ray absorption. A correlation of 0.84 (p = 0.005) was found for a limited number of patients, showing the potential of this technique for the assessment of osteoporosis.
Assuntos
Aumento da Imagem/métodos , Osteoporose/diagnóstico , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/patologia , Tomografia Óptica/métodos , Ulna/diagnóstico por imagem , Ulna/patologia , Ultrassonografia/métodos , Estudos de Viabilidade , Humanos , Osteoporose/diagnóstico por imagem , Osteoporose/patologiaRESUMO
BACKGROUND: In end-stage renal disease, average bone mineral density has been reported to be normal or only modestly reduced, more so in the cortical bone. The purpose of the present study was to explore the potential use of quantitative ultrasound, a method reflecting both quantitative and qualitative properties of bone, in assessing bone status in patients on maintenance haemodialysis. METHODS: We studied 71 patients (age 17-81 years, time on dialysis 0-18 years). The speed of sound waves (tSOS; m/s) propagating along the cortical bone has been determined at the tibial shaft. tSOS results were expressed as Z scores, i.e. units of standard deviations from age- and sex-matched normal mean values, and correlated with relevant clinical and biochemical variables. RESULTS: SOS Z score averaged -2. 0 (range -6.8 to 0.6; P<0.001) and was negative in 93% of the patients. Significant inverse correlations were found between SOS Z score and both time on dialysis (r=-0.52; P<0.0001) and serum PTH (r=-0.39; P=0.0002). Markedly reduced SOS Z score, below -2, was found in 80% of the patients whose PTH levels exceeded 34 pmol/l (five times the upper normal limit), compared with 43% of the patients whose PTH levels were below 34 pmol/l(P=0.04). Compared to patients without bone pain (n=51), subjects with bone pain (n=20) had somewhat lower SOS Z scores -2.5+/-2.0 versus -1.8+/-1.4; P=0. 08), but this could be accounted for by longer time on dialysis. CONCLUSIONS: tSOS is substantially reduced in the majority of haemodialysed patients and is related to time on dialysis and serum PTH level. The clinical value of this novel method needs further exploration.
Assuntos
Osso e Ossos/diagnóstico por imagem , Hormônio Paratireóideo/sangue , Diálise Renal , Acústica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/diagnóstico por imagem , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Tíbia/diagnóstico por imagem , UltrassonografiaRESUMO
Familial dysautonomia (FD) patients suffer from multiple fractures and have reduced bone pain, which defers the diagnosis. The pathogenesis of bone fragility in FD is unknown. This study aimed to characterize bone mineral metabolism and density in FD. Seventy-nine FD patients aged 8 months to 48 years (mean age 13.9 +/- 10.4 years, median 12.3) were studied. Clinical data included weight, height, bone age, weekly physical activity and history of fractures. Bone mineral density (BMD) of the lumbar spine (n = 43), femoral neck (n = 26), total hip (n = 22) and whole body (n = 15) were determined by dual-energy X-ray absorptiometry. Serum 25-hydroxyvitamin D3, osteocalcin, bone alkaline phosphatase (B-ALP), parathyroid hormone and urinary N-telopeptide cross-linked type 1 collagen (NTx) were determined in 68 patients and age- and sex-matched controls. Forty-two of 79 patients (53%) sustained 75 fractures. Twenty-four of 43 patients had a spine Z-score < -2.0, and 13 of 26 had a femoral neck Z-score < -2.0. Mean femoral neck BMD Z-score was lower in patients with fractures compared with those without (-2.5 +/- 0.9 vs -1.5 +/- 1.0, p = 0.01). Mean body mass index (BMI) was 16 kg/m2 in prepubertal patients and 18.4 kg/m2 in postpubertal patients. Bone age was significantly lower than chronological age (75.5 vs 99.3 months in prepubertal patients, p < 0.001; 151 vs 174 in postpubertal patients, p < 0.05). NTx and osteocalcin levels were higher in FD patients compared with controls (400 +/- 338 vs 303 +/- 308, BCE/mM creatinine p < 0.02; 90 +/- 59.5 vs 61.8 +/- 36.9 ng/ml, p < 0.001, respectively). B-ALP was lower in FD patients compared with controls (44.66 +/- 21.8 vs 55.36 +/- 36.6 ng/ml, p < 0.04). Mean spine Z-score was significantly lower in physically inactive compared with active patients (-3.00 +/- 1.70 vs -1.77 +/- 1.3, respectively, p = 0.05). We conclude that fractures in FD patients are associated with reduced BMD. FD patients have increased NTx and osteocalcin. Contributing factors include reduced BMI, failure to thrive and reduced physical activity. Preventive therapy and early diagnosis are essential.
Assuntos
Densidade Óssea/fisiologia , Disautonomia Familiar/fisiopatologia , Osteoporose/fisiopatologia , Absorciometria de Fóton/métodos , Adolescente , Adulto , Determinação da Idade pelo Esqueleto , Fosfatase Alcalina/sangue , Análise de Variância , Biomarcadores , Índice de Massa Corporal , Remodelação Óssea/fisiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Colágeno Tipo I/urina , Disautonomia Familiar/sangue , Disautonomia Familiar/complicações , Feminino , Fraturas Ósseas/etiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteoporose/etiologiaRESUMO
Young ballet dancers are at risk both for osteopenia, due to low body weight, inadequate nutrition and gonadal dysfunction, as well as for lower limbs stress fractures. However, a direct relationship between stress fractures and bone mass in dancers could not be demonstrated, raising the possibility that qualitative aspects of bone, such as elasticity, may be adversely affected in the dancers. To test this hypothesis, speed of sound, a physical parameter that reflects both quantitative and qualitative properties of bone, was determined at the tibial bone of 27 dance students and 27 non-dance students. The results were compared to bone mineral density at the tibia and the lumbar spine, measured by dual-energy x-ray absorptiometry. All three bone measurements were lower in the dance group, but the difference was statistically significant only for the tibial speed of sound. The role of tibial speed of sound measurement in assessing bone status in athletes warrants further exploration.
Assuntos
Dança/fisiologia , Tíbia/diagnóstico por imagem , Absorciometria de Fóton , Adolescente , Estatura , Índice de Massa Corporal , Peso Corporal , Densidade Óssea , Doenças Ósseas Metabólicas/etiologia , Estudos de Casos e Controles , Dança/lesões , Elasticidade , Feminino , Fraturas de Estresse/etiologia , Humanos , Traumatismos da Perna/etiologia , Vértebras Lombares/anatomia & histologia , Vértebras Lombares/diagnóstico por imagem , Distúrbios Menstruais/etiologia , Distúrbios Nutricionais/etiologia , Análise de Regressão , Fatores de Risco , Tíbia/anatomia & histologia , UltrassonografiaRESUMO
To characterize the magnitude and location of mineralized bone loss, 40 patients (20 men, 20 women, 29 white, 11 black) with clinically significant renal osteodystrophy who could be unambiguously classified based on histologic criteria as having osteitis fibrosa (OF; 20 cases) or osteomalacia (OM; 20 cases) were studied; they had been on maintenance hemodialysis for 4.6 +/- 3.0 yr. One hundred forty-two healthy women of similar age and ethnic composition served as control subjects. In all subjects, the proportions of mineralized bone, osteoid, and porosity (nonbone soft tissue) were measured separately in cortical and cancellous bone tissue, from intact full-thickness biopsies of the ilium, representative of the axial skeleton. The results were related to the volumes of cortical and cancellous bone tissue separately and to the volume of the entire biopsy core. Approximately three-quarters of the patients had measurements in the appendicular skeleton by single photon absorptiometry of the radius and morphometry of the metacarpal. Disease effects did not differ significantly between ethnic groups. Mineralized cortical bone volume (per unit of core volume) was reduced by approximately 45% in both patient groups. Mineralized cancellous bone volume was significantly increased by 36% in the patients with OF and nonsignificantly reduced by 9% in the patients with OM; however, the reduction in the latter patients was significant in relation to tissue volume. The combined total deficit for both types of iliac bone was approximately 20% in the patients with OF and approximately 40% in the patients with OM. Significant reductions in appendicular cortical bone were demonstrated in both patient groups at both measurement sites. Regardless of the current histologic classification, the major structural abnormality in the skeleton is generalized thinning of cortical bone due to increased net endocortical resorption, the most characteristic effect on bone of hyperparathyroidism. Protection of the skeleton from the adverse consequences of renal failure will require therapeutic intervention in patients with no symptoms of either renal or bone disease.
Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/patologia , Falência Renal Crônica/complicações , Osteíte Fibrosa Cística/patologia , Osteomalacia/patologia , Diálise Renal , Absorciometria de Fóton , Adolescente , Adulto , Idoso , Análise de Variância , Biópsia por Agulha , Densidade Óssea , Osso e Ossos/patologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Feminino , Humanos , Ílio/patologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Osteíte Fibrosa Cística/etiologia , Osteíte Fibrosa Cística/prevenção & controle , Osteomalacia/etiologia , Osteomalacia/prevenção & controle , Valores de ReferênciaRESUMO
Dosing convenience is a key element in the effective management of any chronic disease, and is particularly important in the long-term management of osteoporosis. Less frequent dosing with any medication may enhance compliance, thereby maximizing the effectiveness of therapy. Animal data support the rationale that once-weekly dosing with alendronate 70 mg (7 times the daily oral treatment dose) could provide similar efficacy to daily dosing with alendronate 10 mg due to its long duration of effect in bone. In addition, dog studies suggest that the potential for esophageal irritation, observed with daily oral bisphosphonates, may be substantially reduced with once-weekly dosing. This dosing regimen would provide patients with increased convenience and would be likely to enhance patient compliance. We compared the efficacy and safety of treatment with oral once-weekly alendronate 70 mg (N=519), twice-weekly alendronate 35 mg (N=369), and daily alendronate 10 mg (N=370) in a one-year, double-blind, multicenter study of postmenopausal women (ages 42 to 95) with osteoporosis (bone mineral density [BMD] of either lumbar spine or femoral neck at least 2.5 SDs below peak premenopausal mean, or prior vertebral or hip fracture). The primary efficacy endpoint was the comparability of increases in lumbar spine BMD, using strict pre-defined equivalence criteria. Secondary endpoints included changes in BMD at the hip and total body and rate of bone turnover, as assessed by biochemical markers. Both of the new regimens fully satisfied the equivalence criteria relative to daily therapy. Mean increases in lumbar spine BMD at 12 months were: 5.1% (95% CI 4.8, 5.4) in the 70 mg once-weekly group, 5.2% (4.9, 5.6) in the 35 mg twice-weekly group, and 5.4% (5.0, 5.8) in the 10 mg daily treatment group. Increases in BMD at the total hip, femoral neck, trochanter, and total body were similar for the three dosing regimens. All three treatment groups similarly reduced biochemical markers of bone resorption (urinary N-telopeptides of type I collagen) and bone formation (serum bone-specific alkaline phosphatase) into the middle of the premenopausal reference range. All treatment regimens were well tolerated with a similar incidence of upper GI adverse experiences. There were fewer serious upper GI adverse experiences and a trend toward a lower incidence of esophageal events in the once-weekly dosing group compared to the daily dosing group. These data are consistent with preclinical animal models, and suggest that once-weekly dosing has the potential for improved upper GI tolerability. Clinical fractures, captured as adverse experiences, were similar among the groups. We conclude that the alendronate 70 mg once-weekly dosing regimen will provide patients with a more convenient, therapeutically equivalent alternative to daily dosing, and may enhance compliance and long-term persistence with therapy.