Efficacy and tolerability of intravenous ibandronate injections in postmenopausal osteoporosis: 2-year results from the DIVA study

OBJECTIVE: An effective and well tolerated intravenous (IV) bisphosphonate could provide a new treatment method for patients with osteoporosis. The Dosing IntraVenous Administration (DIVA) study was designed to identify the optimal ibandronate IV injection schedule for the treatment of postmenopausal osteoporosis by comparing the efficacy and tolerability of 2- and 3-monthly injections with the previously evaluated daily oral ibandronate regimen. We report the effects on lumbar spine and proximal femur bone mineral density (BMD) and bone resorption markers over 2 years. METHODS: This randomized, double-blind, double-dummy, noninferiority study recruited 1395 women (aged 55-80 yrs; > or = 5 yrs since menopause) with osteoporosis [mean lumbar spine (L2-L4) BMD T-score < -2.5 and > or = -5.0]. Patients received IV ibandronate (2 mg every 2 mo or 3 mg every 3 mo) plus daily oral placebo, or 2.5 mg daily oral ibandronate plus 2- or 3-monthly IV placebo. Supplemental vitamin D (400 IU) and calcium (500 mg) were provided throughout the 2-year study. RESULTS: At 2 years, the 2- and 3-monthly IV regimens achieved statistically noninferior and also superior increases in lumbar spine BMD compared with the daily regimen (6.4% and 6.3% vs 4.8%, respectively; p < 0.001). Greater increases were also obtained with IV ibandronate versus daily in proximal femur BMD. Serum concentrations of the biochemical marker of bone resorption C-telopeptide of the alpha-chain of type I collagen were reduced to a similar extent in all treatment arms (53.4%-59.9%). The tolerability profile of the IV regimens was similar to that observed with daily oral therapy. CONCLUSION: Ibandronate IV injections are an effective and well tolerated treatment for postmenopausal osteoporosis and provide a useful alternative to oral dosing.     

Intravenous ibandronate injections given every three months: a new treatment option to prevent bone loss in postmenopausal women

OBJECTIVE: To investigate the efficacy, safety, and dose response of three doses of ibandronate, given intermittently by intravenous (IV) injection every three months, in preventing postmenopausal osteoporosis. PATIENTS AND METHODS: 629 postmenopausal women, categorised according to time since menopause and baseline lumbar spine (L1-4) bone mineral density (BMD), were enrolled into a multicentre, double blind, placebo controlled trial. They were randomly allocated to receive IV ibandronate 0.5 mg, 1 mg or 2 mg, or placebo every three months. All women received daily calcium supplementation. RESULTS: One year's treatment with intermittent IV ibandronate injections produced a dose dependent gain in mean (SD) lumbar spine BMD from baseline of 2.5 (2.5)%, 1.8 (2.6)%, and 1.0 (2.8)% in the groups receiving 2 mg, 1 mg, and 0.5 mg ibandronate, respectively, compared with a loss of BMD of 0.4 (2.4)% in the women in the placebo group; p=0.0001 for each ibandronate dose v placebo. Highest BMD gains occurred in women with osteopenia receiving 2 mg ibandronate. Similarly, at the hip, all three doses of ibandronate produced significantly better gains in BMD than placebo (p<0.05), with the greatest gains in the women with osteopenia receiving the 2 mg dose. Ibandronate concomitantly and dose dependently suppressed markers of bone turnover in comparison with placebo, and injections were well tolerated. CONCLUSION: IV ibandronate injections, given every three months, may be an effective alternative to oral bisphosphonates and hormonal therapy in the prevention of bone loss in postmenopausal women.     

Intravenous ibandronate in men with osteoporosis: an open pilot study over 2 years

In the treatment of osteoporosis, the tolerance of oral bisphosphonates is often low. The high potency of ibandronate allows iv bolus injections that can be repeated every 2 to 3 months. However, the best dose and time interval of the treatment with iv ibandronate is still debated. Efficacy of 2-mg ibandronate injected every 3 months was tested in men with osteoporosis over 2 yr, in a prospective, open study. Fourteen men with primary osteoporosis, mean age 57 +/- 12 yr (range: 40-73), received 2-mg ibandronate iv every 3 months over 2 yr. All got 1 g/day calcium and 880 UI/day vitamin D for 2 yr. Bone mineral density (BMD) increased after 2 yr by 6.7 +/- 1.5% (mean change +/- SEM) at lumbar spine (p<0.001), by 3.2 +/- 08% at trochanter (p<0.001) and by 1.4 +/- 1.1% at femoral neck (ns). Serum beta-crosslaps and osteocalcin decreased significantly by 30-45 and 30%, respectively, during the 2 yr of treatment. Serum calcium increased from the lower to the middle tertile of the normal range during the 2 yr of the study. The observed decrease of bone remodelling and the increase of BMD are of the same magnitude as those described with oral bisphosphonates. The increase of plasma calcium confirms the positive effect of the supplementation with calcium and vitamin D. These results suggest that 3 months are a good interval between two doses of iv ibandronate, when 2 mg are given.     

Intravenous ibandronate injections in postmenopausal women with osteoporosis: one-year results from the dosing intravenous administration study

OBJECTIVE: Although oral bisphosphonates are effective treatments for postmenopausal women with osteoporosis, oral dosing may be unsuitable for some patients. An efficacious intravenously administered bisphosphonate could be beneficial for such patients. Ibandronate, a potent nitrogen-containing bisphosphonate, can be administered using extended dosing intervals, either orally or by rapid intravenous injection. The aim of this study was to identify the optimal intravenous dosing regimen for ibandronate in postmenopausal women with osteoporosis. METHODS: In a randomized, double-blind, double-dummy, phase III, noninferiority study, we compared 2 regimens of intermittent intravenous injections of ibandronate (2 mg every 2 months and 3 mg every 3 months) with a regimen of 2.5 mg of oral ibandronate daily, the latter of which has proven antifracture efficacy. The study group comprised 1,395 women (ages 55-80 years) who were at least 5 years postmenopausal. All patients had osteoporosis (lumbar spine [L2-L4] bone mineral density [BMD] T score less than -2.5). Participants also received daily calcium (500 mg) and vitamin D (400 IU). The primary end point was change from baseline in lumbar spine BMD at 1 year. Changes in hip BMD and in the level of serum C-telopeptide of type I collagen (CTX) were also measured, as were safety and tolerability. RESULTS: At 1 year, mean lumbar spine BMD increases were as follows: 5.1% among 353 patients receiving 2 mg of ibandronate every 2 months, 4.8% among 365 patients receiving 3 mg of ibandronate every 3 months, and 3.8% among 377 patients receiving 2.5 mg of oral ibandronate daily. Both of the intravenous regimens not only were noninferior, but also were superior (P < 0.001) to the oral regimen. Hip BMD increases (at all sites) were also greater in the groups receiving medication intravenously than in the group receiving ibandronate orally. Robust decreases in the serum CTX level were observed in all arms of the study. Both of the intravenous regimens were well tolerated and did not compromise renal function. CONCLUSION: As assessed by BMD, intravenous injections of ibandronate (2 mg every 2 months or 3 mg every 3 months) are at least as effective as the regimen of 2.5 mg orally daily, which has proven antifracture efficacy, and are well tolerated.     

Efficacy and safety of oral weekly ibandronate in the treatment of postmenopausal osteoporosis

Adherence to oral daily bisphosphonate regimens in postmenopausal osteoporosis is currently suboptimal. Less frequent dosing regimens are likely to improve patient adherence and thus, potentially, patient outcomes. A multicenter, randomized, double-blind, noninferiority study was conducted in 235 women (53-80 yr old; time since menopause >/==" BORDER="0"> 3 yr) with postmenopausal osteoporosis [lumbar spine (L1-L4) bone mineral density (BMD) T-score 相似文献   

Intravenous ibandronate injections in postmenopausal women with osteoporosis: One‐year results from the dosing intravenous administration study

Objective

Although oral bisphosphonates are effective treatments for postmenopausal women with osteoporosis, oral dosing may be unsuitable for some patients. An efficacious intravenously administered bisphosphonate could be beneficial for such patients. Ibandronate, a potent nitrogen‐containing bisphosphonate, can be administered using extended dosing intervals, either orally or by rapid intravenous injection. The aim of this study was to identify the optimal intravenous dosing regimen for ibandronate in postmenopausal women with osteoporosis.

Methods

In a randomized, double‐blind, double‐dummy, phase III, noninferiority study, we compared 2 regimens of intermittent intravenous injections of ibandronate (2 mg every 2 months and 3 mg every 3 months) with a regimen of 2.5 mg of oral ibandronate daily, the latter of which has proven antifracture efficacy. The study group comprised 1,395 women (ages 55–80 years) who were at least 5 years postmenopausal. All patients had osteoporosis (lumbar spine [L2−L4] bone mineral density [BMD] T score less than −2.5). Participants also received daily calcium (500 mg) and vitamin D (400 IU). The primary end point was change from baseline in lumbar spine BMD at 1 year. Changes in hip BMD and in the level of serum C‐telopeptide of type I collagen (CTX) were also measured, as were safety and tolerability.

Results

At 1 year, mean lumbar spine BMD increases were as follows: 5.1% among 353 patients receiving 2 mg of ibandronate every 2 months, 4.8% among 365 patients receiving 3 mg of ibandronate every 3 months, and 3.8% among 377 patients receiving 2.5 mg of oral ibandronate daily. Both of the intravenous regimens not only were noninferior, but also were superior (P < 0.001) to the oral regimen. Hip BMD increases (at all sites) were also greater in the groups receiving medication intravenously than in the group receiving ibandronate orally. Robust decreases in the serum CTX level were observed in all arms of the study. Both of the intravenous regimens were well tolerated and did not compromise renal function.

Conclusion

As assessed by BMD, intravenous injections of ibandronate (2 mg every 2 months or 3 mg every 3 months) are at least as effective as the regimen of 2.5 mg orally daily, which has proven antifracture efficacy, and are well tolerated.

     

Alendronate treatment of established primary osteoporosis in men: results of a 2-year prospective study.

Men with osteoporosis have been neglected in the past, and only a few therapeutic trials have been performed in men. The bisphosphonate, alendronate, has been widely used for the treatment of postmenopausal osteoporosis. This prospective, open label, active controlled, randomized clinical study compared the effects of oral alendronate (10 mg daily) and alfacalcidol (1 microg daily) on bone mineral density (BMD), safety, and tolerability in 134 males with primary established osteoporosis. All men received supplemental calcium (500 mg daily). After 2 yr, alfacalcidol-treated patients showed a mean 2.8% increase in lumbar spine BMD (P < 0.01) compared with a mean increase of 10.1% in men receiving alendronate (P < 0.001). The corresponding changes in femoral neck BMD were +2.2% and +5.2% for the alfacalcidol and alendronate groups, respectively (P = 0.009). The incidence rates of patients with new vertebral fractures were 18.2% and 7.4% for the alfacalcidol and alendronate groups, respectively (P = 0.071). Both therapies were well tolerated. Thus, alendronate produced favorable effects on BMD consistent with the results from another study in male osteoporosis. The average increase rates were higher than with alfacalcidol. Alendronate may be superior to alfacalcidol in the treatment of men with established primary osteoporosis.     

Monthly oral ibandronate is effective and well tolerated after 3 years: the MOBILE long-term extension

Oral ibandronate is the first bisphosphonate licensed for once-monthly treatment of postmenopausal osteoporosis. The 2-year Monthly Oral iBandronate In LadiEs (MOBILE) registration study assessed bone mineral density (BMD) and markers of bone turnover and showed that monthly oral ibandronate was at least as effective and well tolerated as a 2.5-mg daily oral regimen. In this study, we report the first year of a long-term extension study to MOBILE and a post hoc analysis of patients receiving 3 years of continuous treatment with monthly ibandronate. Patients who completed MOBILE were eligible for the partially randomized, double-blind extension study and received 100 mg (n = 359) or 150 mg (n = 360) monthly oral ibandronate. A post hoc analysis included patients who received either 100 mg (n = 173) or 150 mg (n = 169) monthly ibandronate continuously throughout the original 2-year MOBILE study and during the first year of the extension study. After one additional year of treatment (total of 3 years), mean lumbar spine BMD increased a further 1.5 and 1.1% in the 150 and 100 mg arms, respectively, compared with 2-year data (original MOBILE study). Total hip BMD changed by 0.3 and -0.08%, respectively. In the post hoc analysis, 3-year increases in lumbar spine BMD were significant in patients receiving ibandronate 150 mg monthly (7.6%; p < 0.0001 vs. baseline) and 100 mg monthly (6.4%; p < 0.0001 vs. baseline). Both groups achieved significant increases in total hip BMD after 3 years compared with baseline (3.4%, 100 mg; 4.1%, 150 mg; p < 0.0001). Serum C-telopeptide of the alpha chain of type I collagen decreased significantly over 3 years' treatment (p < 0.001; all comparisons vs. baseline), remaining within the premenopausal range. Once-monthly oral ibandronate was well tolerated with a low incidence of clinical osteoporotic fractures and upper gastrointestinal events. In conclusion, 150-mg monthly oral ibandronate is an effective and well-tolerated long-term treatment for postmenopausal osteoporosis, with consistent improvement in BMD and bone turnover during 3 years' continuous treatment.     

The use of i. v. bisphosphonate in pregnancy-associated osteoporosis--case study.

OBJECTIVE: Diagnosis of pregnancy-associated osteoporosis is often delayed and therapeutic interventions insufficient. STUDY DESIGN: A 28-year-old patient (BMI=18.6) with no additional risks for osteoporosis experienced acute lumbosacral pain two months postpartum, while lactating. After conservative therapy, thoracic and lumbar spine were X-rayed: severe pregnancy-associated osteoporosis with vertebral fractures was diagnosed. 2-year treatment with i. v. bisphosphonate ibandronate was initiated (2 mg every 3 months) and calcium and vitamin D supplementation. RESULTS: Rapid improvement was observed. Conclusion: In cases with multiple fractures i. v. bisphosphonate leads to substantial decrease of symptoms and further fractures and significant increase of bone mass density (BMD). CONCLUSION: In severe cases of pregnancy-associated osteoporosis with multiple fractures i. v. biphosphonate therapy leads to a decrease of symptoms and fracture risk and an increase of bone mass density (BMD).     

Once-Monthly Ibandronate

Ibandronate is a nitrogen-containing bisphosphonate that has been approved for once-monthly administration in women with post-menopausal osteoporosis. Animal data suggest that the efficacy of the drug is determined by the cumulative dose rather than the frequency of administration. After treatment for 1 year in a large, randomized, double-blind, multicenter trial in women with postmenopausal osteoporosis, once-monthly ibandronate 150 mg was non-inferior to once-daily ibandronate 2.5 mg in terms of increases in mean lumbar spine (primary endpoint) and hip bone mineral density (BMD). In addition, once-monthly ibandronate 150 mg was significantly more effective than once-daily ibandronate for mean increase from baseline in lumbar spine BMD after 1 and 2 years. In another large, randomized, double-blind trial in women with osteoporosis, both once-daily and intermittent (>2-month between-dose interval [not approved]) ibandronate were significantly more effective than placebo in reducing the risk of new vertebral fractures, after treatment for 3 years. Once-daily and intermittent ibandronate also increased mean lumbar spine and hip BMD from baseline by significantly more than placebo. Oral once-monthly, once-daily, and intermittent ibandronate were generally well tolerated. Monthly ibandronate had a similar tolerability profile to once-daily ibandronate. The incidence of adverse events, including gastrointestinal events, with once-daily and intermittent ibandronate did not differ significantly from that with placebo. Significantly more women with osteoporosis preferred once-monthly ibandronate and found it more convenient than once-weekly alendronate, according to data from a 6-month, randomized, open-label, crossover study.     

Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study

BACKGROUND: Reducing bisphosphonate dosing frequency may improve suboptimal adherence to treatment and therefore therapeutic outcomes in postmenopausal osteoporosis. Once-monthly oral ibandronate has been developed to overcome this problem. OBJECTIVE: To confirm the 1 year results and provide more extensive safety and tolerability information for once-monthly dosing by a 2 year analysis. METHODS: MOBILE, a randomised, phase III, non-inferiority study, compared the efficacy and safety of once-monthly ibandronate with daily ibandronate, which has previously been shown to reduce vertebral fracture risk in comparison with placebo. RESULTS: 1609 postmenopausal women were randomised. Substantial increases in lumbar spine bone mineral density (BMD) were seen in all treatment arms: 5.0%, 5.3%, 5.6%, and 6.6% in the daily and once-monthly groups (50 + 50 mg, 100 mg, and 150 mg), respectively. It was confirmed that all once-monthly regimens were at least as effective as daily treatment, and in addition, 150 mg was found to be better (p<0.001). Substantial increases in proximal femur (total hip, femoral neck, trochanter) BMD were seen; 150 mg produced the most pronounced effect (p<0.05 versus daily treatment). Independent of the regimen, most participants (70.5-93.5%) achieved increases above baseline in lumbar spine or total hip BMD, or both. Pronounced decreases in the biochemical marker of bone resorption, sCTX, observed in all arms after 3 months, were maintained throughout. The 150 mg regimen consistently produced greater increases in BMD and sCTX suppression than the 100 mg and daily regimens. Ibandronate was well tolerated, with a similar incidence of adverse events across groups. CONCLUSIONS: Once-monthly oral ibandronate is at least as effective and well tolerated as daily treatment. Once-monthly administration may be more convenient for patients and improve therapeutic adherence, thereby optimising outcomes.     

Intravenous pamidronate compared with oral alendronate for the treatment of postmenopausal osteoporosis

There are several options for the treatment of osteoporosis in postmenopausal women. One of the options is treatment with bisphosphonates, which are very potent inhibitors of osteoclast-mediated bone resorption in vitro and in vivo. The most potent bisphosphonates have a nitrogen side chain and can be given orally or intravenously (i.v.). In the present study we evaluated retrospectively the effect of intravenously administered pamidronate (60 mg monthly) in comparison with oral alendronate with regard to bone mineral density (BMD) and vertebral fractures. A total of 117 consecutive women aged 46 to 78 years were seen in the outpatient clinic because of postmenopausal osteoporosis. Three-year follow-up data were available for a total of 45 patients treated with pamidronate i.v. and 40 patients on alendronate for at least three years. In the pamidronate group mean T score of lumbar spine BMD increased from -3.49 +/- 0.72 to -2.81 +/- 0.74 SDs after three years of treatment (p < 0.001). In the 40 patients treated with alendronate we observed an increase in the T score from -2.95 +/- 0.67 to -2.33 +/- 0.74 SDs (p < 0.001) during the same observation period. X-rays of the lumbar and thoracic spine were analysed from 25 patients in each group who had been treated for at least three years. At baseline nine patients (36%) in the pamidronate group had one or more vertebral fractures compared with seven patients (28%) in the alendronate group. After three years of treatment no new fractures were observed, while only three women in the pamidronate group and two in the alendronate group showed a deterioration of one or more pre-existing vertebral fractures (p = ns between groups). This retrospective analysis demonstrates that monthly intravenous administration of pamidronate is at least as good as alendronate taken orally in the treatment of women with postmenopausal osteoporosis, with regard to improvement of bone mineral density of the lumbar spine. We conclude that it is a good alternative for the more widely used oral bisphosphonates as it is effective, well-tolerated and easy to administer.     

A review of bone pain relief with ibandronate and other bisphosphonates in disorders of increased bone turnover

Several disorders of increased bone turnover and low bone mineral density (BMD) are associated with severe pain that is refractory to treatment with conventional and even opioid analgesics. Because of their ability to effectively improve the underlying pathogenesis of these disorders (i.e., reduce bone resorption and increase BMD), bisphosphonates are considered part of the palliative care of malignant bone-related pain and also appear to have some analgesic efficacy in other, non-malignant conditions. Ibandronate, a potent, nitrogen-containing bisphosphonate that can be given orally and intravenously, has demonstrated robust effects in relieving the pain associated with several malignant disorders. Unlike other available intravenous (i.v.) bisphosphonates, i.v. ibandronate is not associated with renal side effects, even at high doses such as 6 mg every 3 weeks. In addition, oral ibandronate (50 mg daily) is currently the only oral bisphosphonate proven to reduce and maintain bone pain scores below baseline for 2 years in patients with metastatic bone disease. Lower dose, less intense dosing regimens of ibandronate relieve bone pain in non-malignant conditions: i.v. ibandronate (2 mg every 3 months with or without an initial 4 mg injection) provides pain relief for patients with corticosteroid-induced osteoporosis, localised transient osteoporosis (bone marrow oedema) and sternocostoclavicular hyperostosis. Both oral and i.v. ibandronate are well tolerated. In conclusion, ibandronate offers an effective and convenient choice for the relief of bone pain in a wide variety of underlying bone conditions.     

Etidronate prevents high dose glucocorticoid induced bone loss in premenopausal individuals with systemic autoimmune diseases

OBJECTIVE: To assess the efficacy of etidronate and alfacalcidol in preventing glucocorticoid induced bone loss in premenopausal women and men starting high dose glucocorticoid therapy. METHODS: Premenopausal women (n = 16) and men (n = 5) who had just developed autoimmune diseases, and who agreed to use high dose glucocorticoid therapy for the first time, were randomized to receive alfacalcidol (1 micro g/day) alone (alfacalcidol group, n = 11); or alfacalcidol (1 micro g/day) and intermittent cyclical etidronate (200 mg/day for 14 days), given for 4 cycles (combined group, n = 10). They were treated with these medications as well as high dose glucocorticoids for 12 months. RESULTS: In the alfacalcidol group the percentage changes in bone mineral density (BMD) of the lumbar spine after 6 and 12 mo of therapy were -9.6 +/- 0.6% and -10.3 +/- 1.0%, respectively. However, in the combined group the percentage changes in lumbar spine BMD after 6 and 12 mo were -3.8 +/- 1.3% and -4.5 +/- 2.1%. The percentage lumbar spine bone loss rate in the combined group was significantly lower than in the alfacalcidol group at both 6 and 12 mo. After 12 mo the percentage change in femoral neck BMD was increased 2.3 +/- 1.5% in the combined group and was decreased 2.5 +/- 2.4% in the alfacalcidol group; this difference was also statistically significant. There were no significant differences in metabolic bone markers between the groups during the study. CONCLUSION: The results suggest that etidronate could prevent high dose glucocorticoid induced bone loss in premenopausal individuals with systemic autoimmune diseases.     

Oral weekly ibandronate prevents bone loss in postmenopausal women

OBJECTIVES: To investigate the efficacy, safety, and dose-response of once-weekly oral ibandronate in the prevention of postmenopausal bone loss. DESIGN: This was a multi-centre, placebo-controlled, double-blind, randomized, 24-month phase II/III dose-finding study. SETTING: Primary care units in 14 osteoporosis centres. SUBJECTS: A total of 630 women were stratified into four strata according to time since menopause (TSM, 1-3 vs. >3 years) and baseline bone mineral density (BMD; normal: T-score > or =1 vs. osteopenic: -2.5 < or = T-score < or = 1) of the lumbar spine. INTERVENTIONS: Within each stratum women were further randomized to receive once-weekly ibandronate (5, 10, or 20 mg week-1) or placebo for 24 months. MAIN OUTCOME MEASURES: Efficacy parameters were the relative changes from baseline in spine (L1-4) and hip BMD, and biochemical markers of bone turnover (serum and urinary C-telopeptide of collagen type I (CTx), osteocalcin, and alkaline phosphatase) measured by dual energy X-ray absorptiometry and enzyme immunoassays, respectively. RESULTS: Once-weekly therapy with ibandronate induced dose-dependent increases in spine and hip BMD. At month 24, differences between the relative changes in spine and hip BMD induced by 20 mg ibandronate and placebo was 4.0 and 2.7%, respectively. Similar or more pronounced differences were seen in osteopenic women of TSM 1-3 years (5.3 and 3.5%) and of TSM >3 years (3.5 and 2.9%), respectively. A dose-dependent suppression of all biochemical markers of bone turnover was observed with significant decreases in the 20 mg dose groups of all strata at month 24. The overall safety results indicated that once-weekly oral ibandronate was well-tolerated at all three doses. CONCLUSION: Once-weekly oral therapy with 20 mg ibandronate provides an effective and safe therapy for the prevention of postmenopausal bone loss.     

Bone mineral density and quantitative ultrasound in adults with cystic fibrosis

OBJECTIVE: With increasing life span osteoporosis becomes a more recognized problem in patients with cystic fibrosis (CF). The aim of this cross-sectional study in 75 adult patients with CF (mean age 25.3 years) was to assess the prevalence of low bone mineral density (BMD) by dual-energy x-ray absorptiometry (DEXA) and, for the first time, by quantitative ultrasound (QUS), and to identify predicting factors. DESIGN AND METHODS: Bone status was assessed at the lumbar spine (L2-L4) and the femoral neck by DEXA, and at the calcaneus by QUS (stiffness index). These data were correlated with a variety of clinical and anthropomorphic variables. Biochemical markers of bone turnover such as osteocalcin, bone-specific alkaline phosphatase, crosslinks in urine, 25-hydroxy vitamin D (25-OH vitamin D), parathyroid hormone, calcium and free testosterone were determined by standard assays. RESULTS: The mean BMD T score (+/-s.e.m.) was -1.4+/-0.17 at the lumbar spine, and -0.54+/-0.16 at the femoral neck. The mean T score of the calcaneal stiffness index was -0.83+/-0.19. Based on a lumbar spine T score <-2.5 by DEXA, 27% of the patients had osteoporosis. Multiple regression analysis showed that the forced expiratory volume in one second (FEV1) and the use of oral glucocorticoids were independent predictors of low lumbar spine BMD, whereas body mass index (BMI) and the use of oral glucocorticoids were independent predictors of low femoral neck BMD. The stiffness index correlated moderately with BMD (0.49-0.62, P<0.0001). QUS had a sensitivity and specificity of only 57% and 89% respectively for diagnosing 'osteoporosis' (based on a femoral neck T score <-2.5 by DEXA). Positive and negative predictive values were 36% and 95% respectively. CONCLUSIONS: Low BMD is frequent in adults with CF and is most strongly correlated with disease severity (BMI, FEV1) and the use of glucocorticoids. Calcaneal QUS might help to screen out patients with a normal BMD, but sensitivity and specificity were not sufficiently high to replace DEXA in these patients.     

Secondary hyperparathyroidism due to hypovitaminosis D affects bone mineral density response to alendronate in elderly women with osteoporosis: a randomized controlled trial

OBJECTIVES: To determine whether secondary hyperparathyroidism (HPTH) due to hypovitaminosis D affects bone mineral density (BMD) response to alendronate (ALN) in elderly women with osteoporosis. DESIGN: Randomized, controlled trial with 1-year follow-up. SETTING: Two osteoporosis centers in northern Italy. PARTICIPANTS: Community-dwelling women aged 60 and older with a BMD T-score below -2.5 and secondary HPTH with vitamin D insufficiency. INTERVENTION: One hundred twenty subjects were randomly assigned to receive ALN 70 mg once a week alone or ALN 70 mg once a week plus calcitriol (1,25D3) 0.5 microg daily. MEASUREMENTS: BMD measured using dual-energy x-ray absorptiometry at the lumbar spine (L1-L4), femoral neck, and total hip and serum levels of intact PTH at baseline and 12 months. RESULTS: After 1 year, BMD of the lumbar spine, femoral neck, and total hip significantly increased from baseline in both groups (P<.001). Patients allocated to ALN plus 1,25D3 demonstrated a significantly higher increase in lumbar spine BMD than those receiving ALN alone (mean percentage+/-standard deviation 6.8+/-4.6 vs 3.7+/-3.2, P<.001). Serum levels of PTH did not change significantly at 1 year in the ALN group (mean percentage, -3.7+/-27.1, P=.13) but decreased significantly in the ALN plus 1,25D3 group (-32.1+/-22.1, P<.001). At 12 months, subjects with normalized PTH independent of therapy allocation had a greater increase in lumbar spine BMD than those with persistent HPTH (6.5+/-4.6% vs 3.7+/-3.4%, P<.001). Lumbar spine BMD changes showed a significant negative correlation with PTH at 1 year (correlation coefficient (rho) =-0.399, P<.001) and a positive correlation with PTH changes (i.e., baseline value - 1 year value; rho=0.295, P=.005). CONCLUSION: Persistence of secondary HPTH reduces BMD response to ALN in older women with osteoporosis.     

Effects of alendronate on bone mineral density and bone metabolic markers in postmenopausal asthmatic women treated with inhaled corticosteroids

We have recently shown that long-term use of inhaled corticosteroids decreases bone mineral density (BMD) of the lumbar spine in postmenopausal asthmatic women. The present study aimed to evaluate the efficacy of alendronate in comparison with that of alfacalcidol (1-alpha-hydroxyvitamin D(3)) for the treatment of BMD reduction in postmenopausal asthmatic patients who had inhaled corticosteroid therapy without regular use of systemic corticosteroids. Twenty-eight postmenopausal asthmatic patients with BMD T score of -1.0 or less were randomized to receive alendronate (5 mg/d) or alfacalcidol (1 microg/d). Bone mineral density was determined at baseline and 12 months after the treatment, and biochemical markers of bone metabolism were measured at baseline and after 6 and 12 months of treatment. The mean (+/-SD) BMD values at the lumbar spine, the total hip, and the Ward's triangle significantly increased by 4.9 +/- 4.5% (P = .0005), 2.4 +/- 2.2% (P = .0005), and 3.6 +/- 5.2% (P = .02) at 12 months in the alendronate group, whereas the corresponding values did not significantly change in the alfacalcidol group. In the alendronate group, urinary N-telopeptide (NTx), serum osteocalcin, and serum alkaline phosphatase concentrations significantly decreased, and serum intact parathyroid (PTH) level significantly increased, from baseline at both 6 and 12 months. In the alfacalcidol group, urinary NTx showed modest but significant decrease, although the extent of the change was smaller than that in the alendronate group. We concluded that alendronate was effective to improve reduced BMD in postmenopausal asthmatic patients on inhaled corticosteroid therapy through the mechanism of inhibiting bone resorption.     

Effect of alendronate on bone mineral density in male idiopathic osteoporosis

Idiopathic osteoporosis in men is an increasingly recognized disorder accounting for up to 200,000 hip fractures worldwide each year. Although there is no widely accepted or proven efficacious treatment for men with idiopathic osteoporosis, we attempted to examine the effectiveness of alendronate in this disorder. We retrospectively compared the clinical records of male patients with osteopenia (hip or spine T scores less than -1.0, with or without low-trauma fractures) treated either with alendronate 10 mg orally/day and calcium and vitamin D replacement versus conservative treatment with calcium and vitamin D alone. Review included analysis of laboratory studies and bone turnover markers in a subset of patients. We documented bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) and repeated BMD after an average follow-up of 1.9 and 2.7 years in the alendronate-treated and conservative treatment groups, respectively. At baseline, conservatively-treated and alendronate-treated patients had similar BMD at the lumbar spine and hip. Over the period of observation, the conservatively-treated patients exhibited insignificant changes in BMD at all measured sites. In contrast, alendronate treatment resulted in a significant increase in BMD of the spine (+4.6%, P =.002), trochanter (+6.4%, P =.002), and total hip (+4.7%, P =.002). Indeed, compared with conservative treatment, alendronate-treated patients sustained a significant annualized percent increment of the BMD in the spine (2.7 +/- 0.6 v 1.1 +/- 0.3, P =.025), trochanter (4.7 +/- 1.7 v 0.7 +/- 0.6, P =.025), and total hip BMD (3.3 +/- 0.9 v 0.1 +/- 0.4, P =.0009). These data are among the first that illustrate the potential efficacy of alendronate in the management of idiopathic osteoporosis in men.     

Longitudinal analysis of bone mineral density in pre-menopausal female systemic lupus erythematosus patients: deleterious role of glucocorticoid therapy at the lumbar spine

OBJECTIVE: To evaluate whether bone loss occurs over time in pre-menopausal systemic lupus erythematosus (SLE) patients. METHODS: We performed a longitudinal bone mineral density (BMD) analysis in a group of 35 pre-menopausal female SLE patients. Lumbar spine and hip (total and sub-regions) BMDs were measured twice 21 +/- 11 (mean +/- S.D.) months apart by dual-energy X-ray absorptiometry. RESULTS: In the whole cohort of SLE patients, significant bone loss was observed at the lumbar spine (-1.22%/yr) but not at the total hip. Further analyses indicated that lumbar spine bone loss (-2.12%/yr) occurred exclusively in the subgroup of patients who had taken a mean prednisolone daily dose >7.5 mg between the two BMD measurements. Moreover, bone loss was more important in patients who had previously received a cumulative prednisolone dose 7.5 mg.