Hip dysplasia: a significant risk factor for the development of hip osteoarthritis. A cross-sectional survey

OBJECTIVES: The aim of this cross-sectional survey of 2232 women and 1336 men (age range 20-91 yr) was to investigate individual risk factors for hip joint osteoarthritis (OA). METHODS: Standardized, weight-bearing pelvic radiographs were evaluated. Radiological hip joint OA was defined as minimum joint space width (JSW) /=60 yr of age. Of factors entered into logistic regression analyses, only age (P<0.001 for right hips and P<0.001 for left hips) and hip dysplasia (P<0.001 for right hips and P = 0.004 for left hips) were significantly associated with hip OA prevalence in women. In men, only hip dysplasia was associated with hip OA prevalence, P<0.001 in right hips and P = 0.001 in left hips. CONCLUSIONS: Of the individual risk factors investigated in this study, only age and hip dysplasia were associated with the development of hip osteoarthritis.     

Comparison of weekly treatment of postmenopausal osteoporosis with alendronate versus risedronate over two years

OBJECTIVE: A 1-yr extension of the Fosamax Actonel Comparison Trial was completed to compare changes in bone mineral density (BMD), bone turnover, and upper gastrointestinal tolerability over 2 yr of treatment. DESIGN: This was a randomized, double-blind extension conducted at 72 U.S. sites. PATIENTS AND METHODS: Of the 1053 women who completed yr 1, 833 postmenopausal women with low BMD entered the extension, continuing their same treatment allocation [once-weekly (OW) alendronate 70 mg or OW risedronate 35 mg]. Changes in BMD at the hip trochanter, total hip, femoral neck, and lumbar spine and in markers of bone turnover were compared at 24 months. Tolerability was assessed by adverse experience reporting. RESULTS: Alendronate produced greater increases from baseline in BMD at 24 months than did risedronate at the trochanter (alendronate, 4.6%; risedronate, 2.5%, P < 0.001) as well as at all other BMD sites. Significantly more alendronate than risedronate patients had measured BMD increases of 0% or more and 3% or more at all BMD sites (P < 0.001), and fewer alendronate patients had measured decreases of 3% or more at all BMD sites. Significantly greater reductions in all biochemical markers of bone turnover occurred with alendronate, compared with risedronate. No differences were seen in occurrence or discontinuations due to upper gastrointestinal adverse experiences. CONCLUSIONS: Patients receiving 70 mg OW alendronate had greater gains in BMD, were more likely to maintain or gain BMD, and had greater reductions in bone turnover markers than patients receiving 35 mg OW risedronate after 24 months, with no differences in upper gastrointestinal tolerability.     

AVASCULAR NECROSIS OF THE HIP IN SYSTEMIC LUPUS ERYTHEMATOSUS: THE ROLE OF MAGNETIC RESONANCE IMAGING

The value of magnetic resonance imaging (MRI) in the early diagnosisof avascular necrosis (AVN) of the hip in SLE was investigated. Twenty females with severe SLE were studied prospectively. Eachunderwent 6-monthly X-rays, technetium -99m (Tc-99m) pyrophosphatebone scans and MRI of the hips over a 3-yr period. AVN was diagnosed in five hips of three patients (15%) duringthe study period. It was confirmed histologically in three hipsof two patients who underwent core decompression. Radiologicalevidence of AVN was present in two patients at diagnosis. Onepatient developed progressive radiological changes despite coredecompression. Bone scintigraphy was abnormal at some stagein all three patients with AVN however failed to detect theearly ischaemic stage of AVN. MRI was the most reliable investigation and was able to detectasymptomatic AVN prior to the appearance of radiological orscintigraphic abnormalities. KEY WORDS: Osteonecrosis, Core decompression, Femur     

Progression of radiographic hip osteoarthritis over eight years in a community sample of elderly white women

OBJECTIVE: To describe progression over 8 years in a community-based sample of elderly women with radiographic findings of hip osteoarthritis (RHOA) with or without hip pain. METHODS: Baseline and followup anteroposterior pelvic radiographs were obtained at a mean +/- SD 8.3 +/- 0.4 years of followup in women age > or =65 years at the baseline examination of the Study of Osteoporotic Fractures. We evaluated progression in 936 hips of 745 women with one or more baseline findings of RHOA: summary OA grade > or =2, minimum joint space (MJS) < or =1.5 mm, definite femoral or acetabular osteophytes, definite superolateral joint space narrowing (JSN), or moderate or worse superomedial JSN. We separately examined progression in hips with an MJS between 1.5 mm and 2.5 mm. Hip pain and lower extremity disability were assessed by questionnaire and examination. Measures of progression included an increase in summary grade of radiographic findings, increase in total osteophyte score, decrease in MJS of > or =0.5 mm, total hip replacement (THR), and increase in lower extremity disability score. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for baseline radiographic predictors of progression were estimated using general estimating equations. RESULTS: During followup, 12.9% of women with baseline RHOA underwent THR, and 22.8% had substantial worsening of lower extremity disability, while 64.6% of hips with RHOA showed radiographic progression or were replaced. Progression was greater by all measures in the 37% of hips and 47% of women with both RHOA and hip pain at baseline. Of hips with pain, 23.6% progressed to THR compared with 2.7% of hips without pain (OR 8.1 [95% CI 4.2, 15.4], P < 0.001), and MJS decreased > or =0.5 mm in 53.7% of hips with pain compared with 30.7% of hips without pain (OR 1.9 [95% CI 1.4, 2.6], P < 0.001). Women with hip pain were more likely to have worsened lower extremity disability (29.3% versus 17.6%; OR 1.8 [95% CI 1.2, 2.8], P = 0.0053). Hips with an MJS >1.5 mm and < or =2.5 mm (n = 1,868) had primarily superomedial narrowing and comparatively low rates of progression that did not differ by hip pain. Femoral osteophytes, superolateral JSN, and subchondral bone changes were independent predictors of progression. CONCLUSION: Among women recruited from the community, radiographic and clinical progression was greater in those with symptomatic RHOA, but still substantially less frequent than previously reported for hip OA patients in clinical settings. Asymptomatic RHOA and hips with an isolated finding of mild JSN (MJS of 1.5 mm to 2.5 mm) were unlikely to progress over 8 years.     

Core decompression in avascular necrosis of the hip in sickle-cell disease

Sickle-cell disease (SCD) is the most common cause of avascular necrosis (AVN) of the hip in childhood. It results in significant physical impairment and chronic pain, and often progresses to require hip replacement. Conservative therapy is ineffective. We evaluated whether core decompression can arrest progression of AVN. We performed 13 coring procedures in 10 patients with SCD and AVN. Patients ranged from age 9–21 years at diagnosis (mean, median age, 15 years); five hips were stage I, six hips were stage II, and two hips were stage III. Mean follow-up on these patients was 3.7 years. Efficacy of the procedure was evaluated by clinical improvement in pain, radiographic progression, and need for further surgery. All 5 stage I patients had substantial improvement in pain, and only one showed X-ray progression. Five of the 6 (83%) stage II patients had improvement in pain, and 2 patients progressed on X-ray. Both stage III patients progressed on X-ray, but one was clinically improved. None of the 10 patients has required further surgery. Our results demonstrate that in early AVN, core decompression was beneficial for almost all patients, even with progression on X-ray. Core decompression should be considered in the management of SCD patients with early AVN. © 1996 Wiley-Liss, Inc.     

Alendronate in early postmenopausal women: effects on bone mass during long-term treatment and after withdrawal. Alendronate Osteoporosis Prevention Study Group

We studied the effect on bone mass of alendronate treatment for 5 yr and its withdrawal. Four hundred and forty-seven postmenopausal women with normal bone mass entered a 3-yr randomized trial followed by a 2-yr open label extension. Three hundred and eleven women completed the first 3 yr, and 263 consented to continue and completed the extension. We are reporting data from groups using the dose of alendronate currently approved for osteoporosis prevention (5 mg) or from the group in which alendronate treatment was withdrawn: 52 women received alendronate (5 mg) for 5 yr (group I), 56 received 3 yr of placebo followed by alendronate (5 mg) for 2 yr (group II), and 52 received alendronate (20 mg) for 2 yr followed by 3 yr off therapy (group III). In group I, alendronate (5 mg) increased bone mineral density (BMD) at the spine and trochanter by 2.5-3.2% (P < 0.001 vs. baseline) and stabilized total body and femoral neck BMD (change vs. baseline, P = NS) over 5 yr. By the end of 5 yr, BMD was comparable at the spine, hip, and total body in groups I and III. The 3-yr decrease in BMD after withdrawal of alendronate (20 mg) in group III was 1.8-5.7% (P < 0.01 vs. baseline) and similar to the 3-yr decrease in BMD in group II during the initial 3 yr. In conclusion, alendronate (5 mg) for 5 yr or alendronate (20 mg) for 2 yr followed by 3 yr off therapy prevented postmenopausal bone loss. After withdrawal of alendronate (20 mg), bone loss resumed at the normal early postmenopausal rate.     

Alendronate increases bone mass and reduces bone markers in postmenopausal African-American women

Previous studies indicated that aminobisphosphonate alendronate sodium, a potent inhibitor of bone resorption, increases bone mineral density (BMD) at the hip and spine, reduces markers of bone turnover, and reduces the risk of fractures in Caucasian postmenopausal women. The purpose of the present study was to investigate whether alendronate increases BMD and reduces markers of bone turnover in African-American postmenopausal women. In a multicenter, randomized, double-blind, placebo-controlled study, 65 African-American women, aged 45 to 88 yr, were randomly assigned to either placebo (n = 33) or alendronate 10 mg daily (n = 32) for 2 yr. Mean BMD T scores of the lumbar spine at baseline were -3.18 in the placebo-treated group and -3.09 in the alendronate-treated group. All women took 500 mg elemental calcium daily in the form of calcium carbonate and 500 IU vitamin D. Alendronate significantly increased BMD and reduced markers of bone formation and resorption, compared with placebo. At 2 yr, mean changes +/- SE in BMD were 6.5% +/- 0.7% for the lumbar spine (P < 0.001), 4.5% +/- 1.0% for the femoral neck (P < 0.001), 6.4% +/- 0.6% for the femoral trochanter (P < 0.001), 4.1% +/- 0.7% for the total hip (P < 0.001), 0.7% +/- 0.5% for the one third forearm (NS), and 2.0% +/- 0.4% for the total body (P < 0.001) in women treated with alendronate, compared with 0.9% +/- 0.6% (NS), 0.5% +/- 1.1% (NS), -0.2 +/- 0.8 (NS), -1.1 +/- 0.7% (NS), -0.8% +/- 0.6% (NS), and -1.2% +/- 0.6% (P < 0.05) for the lumbar spine, femoral neck, trochanter, total hip, one third forearm, and total body, respectively, in women treated with placebo. At 2 yr, mean serum bone-specific alkaline phosphatase had declined by 46.3% with alendronate (P < 0.001) and 13.6% with placebo (P < 0.01), and mean urinary N-telopeptide of type I collagen/creatinine ratio had declined by 70.5% with alendronate (P < 0.001) and 6.7% with placebo (NS). The incidence of adverse experiences was not different between the two groups. We conclude that in postmenopausal African-American women with osteoporosis, alendronate, 10 mg daily for 2 yr, increases BMD at the lumbar spine, hip, and total body and reduces markers of bone remodeling and is well tolerated.     

Outcome of total hip replacement for avascular necrosis in systemic lupus erythematosus

OBJECTIVE: To describe the short and medium term results of total hip arthroplasty (THA) for avascular necrosis in patients with systemic lupus erythematosus (SLE). METHODS: Nineteen patients with SLE and avascular necrosis of the femoral head (AVNFH), who underwent 26 THA were retrospectively reviewed with a minimum followup of 2 years. To determine whether these patients had results similar to those of patients with other conditions, we formed a control group of 19 patients who had 29 THA. They were matched for age, sex, and followup to the patients with SLE. Controls had THA for juvenile rheumatoid arthritis (n = 7), osteoarthritis (5), adult onset rheumatoid arthritis (8), developmental dysplasia of the hip (4), and other diagnoses (5). Outcome measures included a 10 point visual analog scale (VAS) for pain, the Harris hip score, and the SF-36 self-administered health outcome questionnaire. We used the methods of Delee, Harris, and Engh for radiological assessment. RESULTS: Mean age at surgery was 46 years (range 21-71 years) and average followup was 4 years, 7 months (range 1 yr 9 mo to 9 yrs 6 mo), similar in both groups. Technical problems, mostly consisting of small, nonpropagating cracks of the calcar in uncemented stems, were encountered in 4 SLE hips and 1 control hip. Six complications were noted in the SLE group, including 2 early, nonrecurrent dislocations, 1 patient with thigh pain for 1 year, 1 pericarditis, 1 sick-sinus syndrome, and 1 urinary tract infection. There was one case of urinary tract infection in the control group. One SLE patient developed a low grade prosthetic infection and underwent successful revision 2 years after primary surgery. Clinical outcome measures had similar scores in the 2 groups: average VAS pain score = 2.00 in SLE hips (maximum 10) and 1.97 in control hips; mean Harris hip score = 86.7 in SLE patients (maximum 100) and 81.9 in controls; average SF-36 score = 63.4 in SLE patients (maximum 100) and 60.5 in controls. There was no radiological evidence of implant loosening in controls; there was 1 asymptomatic cup migration in the SLE group. CONCLUSION: In the short and medium term, patients with SLE and AVN had good results after THA. Results were similar in patients who had hip replacement for other diagnoses. Less favorable clinical outcomes of hip replacement have been reported in young patients who have AVN of other etiology (e.g., alcoholic, post-traumatic), but this was not the case in our young patients who had AVN and SLE. Thus, AVNFH and SLE should not constitute a contraindication to hip replacement.     

Early treatment of avascular necrosis in systemic lupus erythematosus.

Avascular necrosis (AVN) of the hips is associated with significant disability, and the majority of established cases require major surgery. In a retrospective analysis of 185 patients with systemic lupus erythematosus (SLE) 13 (7%) were found to have AVN. Of these, six had Raynaud's phenomenon, all had been on corticosteroids, and one had digital vasculitis. The mean duration of corticosteroid therapy was two years (range four months to five years). Five patients developed AVN two to 10 years after discontinuing steroids. The mean duration of disease at the onset of AVN was 6.85 years (range 1-19 years), and the mean age at onset of AVN was 31 years. Ten patients had severe multisystem involvement. None of the patients abused alcohol. Surgery was performed on 11 hips. Three had total hip replacement for stages 3 and 4 and seven had core decompression for stages 1 and 2. AVN progressed in two (28%) of these patients. In another patient core decompression failed for technical reasons. She subsequently required total hip replacement. The early detection of AVN to avoid the need for major surgery is stressed.     

Outcome of total hip arthroplasty for avascular necrosis of femoral head in systemic lupus erythematosus patients: A comparative study

BackgroundAvascular necrosis (AVN) is a major cause of disability in systemic lupus erythematosus (SLE) patients which directly affects the functionality and quality of life. Total hip arthroplasty (THA) is indicated for severe cases with major disability and severe pain. It is still debatable if SLE is an independent risk factor for poor outcome in THA or not.Aim of the workTo evaluate the result of THA for AVN of the femur head in SLE patients.Patients and methods22 THAs were performed in 20 SLE patients and were compared with the results of 25 hips of 22 patients who had THA due to AVN with non-SLE conditions. All patients were followed up after the surgery at 6 weeks, 3, 6 and 12 months post-operatively, and then yearly for functional and radiological outcomes.ResultsThe Harris hip score (HHS) increased from a preoperative average of 26 points to 93.52 at the most recent follow-up. In the control group, the mean HHS was 26 preoperatively and 95.52 postoperatively at the last follow-up. Visual analog scale for pain (VAS pain) decreased from 8 in SLE and 6 in the non-SLE group to 2 and 1 respectively. No significant difference was found between SLE patients and non-SLE patients regarding complications except for more chest infections in the SLE group. No mortality was recorded in both groups in the postoperative follow-up period of a mean of thirty months.ConclusionTHA outcome is as favorable in AVN patients with SLE as in non-SLE.     

Avascular osteonecrosis after treatment of SARS: a 3-year longitudinal study

Objective  To investigate the relationship between avascular osteonecrosis (AVN) and corticosteroid treatment given to patients with severe acute respiratory syndrome (SARS).
Methods  Longitudinal study of 71 former SARS patients (mainly health care workers) who had been treated with corticosteroids, with an observation time of 36 months. Magnetic resonance images (MRI) and X-rays of hips, knees, shoulders, ankles and wrists were taken as part of the post-SARS follow-up assessments.
Results  Thirty-nine per cent developed AVN of the hips within 3–4 months after starting treatment. Two more cases of hip necrosis were seen after 1 year and another 11 cases of AVN were diagnosed after 3 years, one with hip necrosis and 10 with necrosis in other joints. In total, 58% of the cohort had developed AVN after 3 years of observation. The sole factor explaining AVN in the hip was the total dose of corticosteroids received.
Conclusion  The use of corticosteroids in SARS has been debated; opinions conflict about whether the immediate benefits in terms of saving lives compensate for the adverse effects, including AVN.     

Clinical effectiveness and dose response of image-guided intra-articular corticosteroid injection for hip osteoarthritis

OBJECTIVES: To assess symptomatic change after intra-articular corticosteroid (IAST) injection at 2 doses in hip osteoarthritis (OA), and to examine dose response and predictors of response. METHODS: Patients with hip OA (90 women and 30 men and median age 64 yrs) referred for IAST fluoroscopic injection were included in this longitudinal, clinical trial. WOMAC scores, body mass index (BMI), conventional radiographic grade (Kellgren and Lawrence scoring) and ultrasound measures (including capsular thickness and osteophyte assessments) were recorded at baseline. In the first phase of the study, 75 patients were injected with 40 mg methylprednisolone; another 45 patients were injected with 80 mg in the second phase. Change in WOMAC scores from baseline to weeks 6 and 12 were calculated for each dose and then dose comparisons were made. Clinical responders (>15% reduction in baseline pain score) were identified in order to establish predictors of response. RESULTS: For the 40 mg dose, there was a statistically significant improvement in pain (P < 0.001) and stiffness (P < 0.001) but not disability at week 6, and only the improvement in stiffness at week 12 was maintained (P = 0.041). For the 80 mg dose, there was significant improvement in pain (P < 0.001), stiffness (P < 0.001) and disability (P < 0.001) at week 6, which was maintained for all domains at week 12 (P = 0.002; P = 0.001; P < 0.001). When the doses were compared, the 80 mg dose demonstrated a significant improvement compared with the 40 mg group for stiffness at week 12 (P = 0.026) and disability at both weeks 6 and 12 (P = 0.026; P = 0.004). Imaging findings did not relate to severity of symptoms or response to IAST. CONCLUSIONS: In these two hip OA cohorts, both the 40 mg and 80 mg IAST doses had a beneficial effect at week 6, while the 80 mg dose maintained this improvement at week 12. Comparison of the two dose groups provided some evidence of a dose response. Randomized controlled trials of IAST for hip OA are now required.     

Asymptomatic avascular necrosis in patients with primary antiphospholipid syndrome in the absence of corticosteroid use: a prospective study by magnetic resonance imaging

OBJECTIVE: To evaluate the prevalence of avascular necrosis (AVN), using magnetic resonance imaging (MRI), in patients with primary antiphospholipid syndrome (APS) and in patients with systemic lupus erythematosus (SLE), with or without anticardiolipin antibodies (aCL), who are asymptomatic for AVN and have not taken corticosteroids. METHODS: Seventy-nine subjects who were asymptomatic for AVN were evaluated by MRI of the femoral heads: 30 patients with primary APS who had never received corticosteroids, 19 SLE patients who had never received steroids (divided into 2 groups, aCL positive and aCL negative, in order to examine any association between AVN and aCL), and 30 healthy subjects who were age- and sex-matched with patients with primary APS. Established MRI criteria were used for a diagnosis of AVN. RESULTS: Asymptomatic AVN was evident in 6 (20%) of 30 patients with primary APS: 3 of them (1 man, 2 women) had intermediate bilateral AVN, and 3 (all women) had early AVN (bilateral in 1 patient). Results of hip and pelvis radiography and dynamic scintigraphy were negative. Followup MRI 6 months later revealed no changes. At the time of the initial MRI examination, the mean (+/-SD) age of patients in whom AVN was identified was 31.2 +/- 7.3 years, and that of patients without AVN was 42.4 +/- 11.9 years (P = 0.036). Livedo reticularis occurred significantly more commonly in the group with AVN (P = 0.041). None of the healthy subjects and none of the patients with SLE demonstrated AVN on MRI. CONCLUSION: AVN can be detected by MRI in 20% of patients with primary APS. Younger patients tend to develop AVN more frequently than do older patients, and the presence of livedo reticularis may identify individuals at risk for AVN. Clinicians should be aware of this possible clinical manifestation of primary APS, because early diagnosis can lead to early intervention.     

Effects of alendronate and hormone replacement therapy, alone and in combination, on bone mass and markers of bone turnover in elderly women with osteoporosis

The aim of the study was to compare alendronate, hormone replacement therapy (HRT), and their combination in treatment of osteoporosis in elderly postmenopausal women. Ninety patients, aged 65-80 yr (mean 71), with a T-score of bone mineral density (BMD) of 2.5 or less at either the lumbar spine or the femoral neck were randomized to receive daily 10 mg alendronate (n = 30), 2 mg estradiol plus 1 mg norethisterone acetate (n = 30) (HRT), or their combination (n = 30) for 2 yr. BMD of the lumbar spine and the upper femur was measured at baseline and after 1 and 2 yr of treatment. Urinary excretion of type I collagen aminoterminal telopeptide as related to creatinine and serum type I procollagen aminoterminal propeptide was assayed at baseline and at 6-month intervals thereafter. Increases of 9.1-11.2% in lumbar spine BMD at 2 yr were similar in the study groups. Only HRT increased femoral neck BMD statistically significantly (P < 0.0001 for a change from baseline) at both 1 (+4.9%; P =NS vs. the other groups) and 2 yr (+5.8%; P < 0.05 vs. the other groups). Total hip BMD increased similarly in all study groups. Percentage reductions in urinary type I collagen aminoterminal telopeptide in the HRT group (60.2-62.7%) were significantly smaller than those in the combination group (78.1-80.4%) (P < 0.0001-0.0069) and the alendronate-only group (72.4-76.1%) (P = 0.047 at 24 months). Serum type I procollagen aminoterminal propeptide decreased less in the HRT group (53.6-59.8%) than in the other groups [73.0-75.0% in the alendronate group (P < 0.001 at 12 months); 67.0-71.5% in the combination group (P < 0.0001 at 12 months, P = 0.013 at 24 months)]. We conclude that in elderly postmenopausal women with osteoporosis, the combination of HRT and alendronate did not offer an extra gain of bone mass over either treatment alone. In terms of BMD changes, the single treatments were equally effective, but the reductions in bone markers were less with HRT than with alendronate.     

Clinical assessment and core outcome variables are poor predictors of hip arthritis diagnosed by MRI in juvenile idiopathic arthritis

OBJECTIVES: To compare the diagnostic performance of clinical assessment against magnetic resonance imaging (MRI) diagnosed hip arthritis in a juvenile idiopathic arthritis (JIA) population. To determine the clinical and serological predictors of MRI diagnosed hip arthritis. METHODS: A total of 34 JIA patients with established disease (mean disease duration 6.3 yrs) had their hip MRIs scored for features of active hip arthritis and hip damage. Results were compared with clinical variables (disease subtype, history of hip pain, core outcome variables (COV)) and the clinician's assessment of active hip arthritis. RESULTS: MRI features of active hip arthritis were found in 45 hips (70%) and hip damage in 36 hips (56%). Clinical assessment had fair agreement with MRI scoring of active arthritis in patients with disease duration <4 yrs (kappa score 0.38, P = 0.045). Clinical assessment had a sensitivity of 25.7% and specificity of 91% for detecting MRI diagnosed arthritis. Of the core outcome variables only erythrocyte sedimentation rate predicted inflammation detected on MRI (r = 0.44, P = 0.014). CONCLUSIONS: The association between the clinician's assessment, core outcome variables and MRI findings in this study was limited. This indicates that clinical and laboratory findings are inadequate diagnostic tools for the assessment of hip arthritis when compared with MRI as the gold standard.     

Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women

OBJECTIVE: To review the effect of alendronate on bone density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE, EMBASE, Current Contents, and the Cochrane Controlled trials registry from 1980 to 1999, and we examined citations of relevant articles and proceedings of international meetings. STUDY SELECTION: We included 11 trials that randomized women to alendronate or placebo and measured bone density for at least 1 yr. DATA EXTRACTION: For each trial, three independent reviewers assessed the methodological quality and abstracted data. DATA SYNTHESIS: The pooled relative risk (RR) for vertebral fractures in patients given 5 mg or more of alendronate was 0.52 [95% confidence interval (CI), 0.43-0.65]. The RR of nonvertebral fractures in patients given 10 mg or more of alendronate was 0.51 (95% CI 0.38-0.69), an appreciably greater effect than for the 5 mg dose. We found a similar reduction in RR across nonvertebral fracture types; in particular, RR reductions for fractures traditionally thought to be "osteoporotic," such as hip and forearm, were very similar to RR reductions for "nonosteoporotic" fractures. Individual studies showed similar results, reflected in the P values of the test of heterogeneity (P = 0.99 for vertebral and 0.88 for nonvertebral fractures). Alendronate produced positive effects on the percentage change in bone density, which increased with both dose and time. After 3 yr of treatment with 10 mg of alendronate or more, the pooled estimate of the difference in percentage change between alendronate and placebo was 7.48% (95% CI 6.12-8.85) for the lumbar spine (2-3 yr), 5.60% (95% CI 4.80-6.39) for the hip (3-4 yr), 2.08% (95% CI 1.53-2.63) for the forearm (2-4 yr), and 2.73% (95% CI 2.27-3.20) for the total body (3 yr). Heterogeneity of the treatment effect of alendronate was not consistently explained by any of our a priori hypotheses; in particular, the effect was very similar in prevention and treatment studies. The pooled RR for discontinuing medication due to adverse effects for 5 mg or greater of alendronate was 1.15 (95% CI 0.93-1.42). The pooled RR for discontinuing medication due to gastro-intestinal (GI) side effects for 5 mg or greater was 1.03 (0.81-1.30, P = 0.83), and the pooled RR for GI adverse effects with continuation of medication was 1.03 (0.98 to 1.07) P = 0.23. CONCLUSIONS: Alendronate increases bone density in both early postmenopausal women and those with established osteoporosis while reducing the rate of vertebral fracture over 2-3 yr of treatment. Reductions in nonvertebral fractures are evident among postmenopausal women without prevalent fractures and have bone mineral density (BMD) levels below the World Health Organization threshold for osteoporosis. The impact on fractures appears consistent across all fracture types, casting doubt on traditional distinctions between osteoporotic and nonosteoporotic fractures.     

Early changes in serum N-telopeptide and C-telopeptide cross-linked collagen type 1 predict long-term response to alendronate therapy in elderly women

The aim of this study was to determine whether early changes in serum markers of bone resorption could predict long-term responses in bone mineral density (BMD) after alendronate therapy in elderly women. One hundred and twenty women (mean age, 70 yr) were randomized to alendronate or placebo in this double blind, placebo-controlled clinical trial for 2.5 yr. Outcome measures were hip and spine BMD and biochemical markers of bone resorption, including serum N-telopeptide and C-telopeptide cross-linked collagen type I (NTx and CTx, respectively). Serum NTx and CTx were highly correlated at baseline (r = 0.73; P < 0.001) and remained so throughout the study (range, r = 0.36-0.56; all P < 0.05). After treatment with alendronate, serum NTx decreased 30.4+/-16.0% at 6 months, reaching a nadir of -36.7+/-18.0% by 24 months (P < 0.001). Serum CTx decreased 43.5+/-67.0% at 6 months and continued to decrease to 67.3+/-19.3% at 2.5 yr (P < 0.001). Moreover, decreases in serum NTx and CTx at 6 months were correlated with long-term improvements in vertebral BMD at 2.5 yr in patients receiving alendronate therapy (NTx: r = -0.42; CTx: r = -0.31; both P < 0.05). We conclude that early changes in serum NTx and CTx, markers of bone resorption, predict long-term changes in vertebral BMD in elderly women receiving alendronate therapy and provide a useful tool to assess skeletal health.     

Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women

This study compared the effects of oral alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. Women at least 5 yr postmenopause (n = 299) were randomized to either 10 mg alendronate, matching alendronate placebo, or open-label intranasal calcitonin 200 IU daily for 12 months. Hip and spine bone mineral density (BMD) and markers of bone turnover were measured, and safety and tolerability were assessed. Alendronate produced greater increases in BMD than calcitonin at 12 months at the lumbar spine (5.16% vs. 1.18%; P < 0.001), trochanter (4.73% vs. 0.47%; P < 0.001), and femoral neck (2.78% vs. 0.58%; P < 0.001). Changes in BMD with calcitonin were greater than with placebo at the femoral neck, but were not different from placebo at either the trochanter or lumbar spine. Greater decreases in bone turnover were seen with alendronate than with calcitonin (serum bone-specific alkaline phosphatase, 43% vs. 9%, P < 0.001; urinary N-telopeptide, 62% vs. 11%, P < 0.001). Similar percentages of patients in each group reported an adverse experience during the study. We conclude that, in postmenopausal women with osteoporosis, 12 months of therapy with alendronate produced significantly greater increases in BMD of the hip and spine and greater decreases in bone turnover than intranasal calcitonin.     

Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial

Primary hyperparathyroidism (PHPT) is often associated with reduced bone mineral density (BMD). A randomized, double-blind, placebo-controlled trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with PHPT. Eligible patients had asymptomatic PHPT and did not meet surgical guidelines or refused surgery. Forty-four patients randomized to placebo or active treatment arms were stratified for gender. At 12 months, patients taking placebo crossed over to active treatment. All patients were on active treatment in yr 2. The primary outcome index, BMD, at the lumbar spine (LS), femoral neck, total hip, and distal one third radius was measured every 6 months by dual-energy x-ray absorptiometry. Calcium, phosphorous, PTH, bone-specific alkaline phosphatase (BSAP) activity, urinary calcium, and urinary N-telopeptide (NTX) excretion were monitored every 3 months. Treatment with alendronate over 2 yr was associated with a significant (6.85%; micro(d) = 0.052; +/-0.94% se; P < 0.001) increase in LS BMD in comparison with baseline. Total hip BMD increased significantly at 12 months with alendronate by 4.01% (micro(d) = 0.027; +/-0.77% se; P < 0.001) from baseline and remained stable over the next 12 months of therapy. BMD at the one third radius site did not show any statistically significant change in the alendronate-treated group at 12 or 24 months of therapy. At 24 months, the alendronate-treated group showed a 3.67% (micro(d) = 0.022; +/-1.63% se; P = 0.038) gain in bone density at the femoral neck site in comparison with baseline. The placebo group, when crossed over to alendronate at 12 months, showed a significant change of 4.1% (micro(d) = 0.034; +/-1.12% se; P = 0.003) in the LS BMD and 1.7% (micro(d) = 0.012; +/-0.81% se; P = 0.009) at the total hip site in comparison with baseline. There was no statistically significant change seen in the placebo group at 12 months at any BMD site and no significant change at 24 months for the distal one third radius or femoral neck sites. Alendronate was associated with marked reductions in bone turnover markers with rapid decreases in urinary NTX excretion by 66% (micro(d) = -60.27; +/-13.5% se; P < 0.001) at 3 months and decreases in BSAP by 49% at 6 months (micro(d) = -15.98; +/-6.32% se; P < 0.001) and by 53% at 9 and 12 months (micro(d) = -17.11; +/-7.85% se; P < 0.001; micro(d) = -17.36; +/-6.96% se; P < 0.001, respectively) of therapy. In the placebo group, NTX and BSAP levels remained elevated. Serum calcium (total and ionized), PTH, and urine calcium did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS at 12 and 24 months from baseline values. Significant reductions in bone turnover occur with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in asymptomatic PHPT among those with low BMD.     

Addition of alendronate to ongoing hormone replacement therapy in the treatment of osteoporosis: a randomized, controlled clinical trial.

Alendronate and estrogen are effective therapies for postmenopausal osteoporosis, but their efficacy and safety as combined therapy are unknown. The objective of this study was to evaluate the addition of alendronate to ongoing hormone replacement therapy (HRT) in the treatment of postmenopausal women with osteoporosis. A total of 428 postmenopausal women with osteoporosis, who had been receiving HRT for at least 1 yr, were randomized to receive either alendronate (10 mg/day) or placebo. HRT was continued in both groups. Changes in bone mineral density (BMD) and biochemical markers of bone turnover were assessed. Compared with HRT alone, at 12 months, alendronate plus HRT produced significantly greater increases in BMD of the lumbar spine (3.6% vs. 1.0%, P < 0.001) and hip trochanter (2.7% vs. 0.5%, P < 0.001); however, the between-group difference in BMD at the femoral neck was not significant (1.7% vs. 0.8%, P = 0.072). Biochemical markers of bone turnover (serum bone-specific alkaline phosphatase and urine N-telopeptide) decreased significantly at 6 and 12 months with alendronate plus HRT, and they remained within premenopausal levels. Addition of alendronate to ongoing HRT was generally well tolerated, with no significant between-group differences in upper gastrointestinal adverse events or fractures. This study demonstrated that, in postmenopausal women with low bone density despite ongoing treatment with estrogen, alendronate added to HRT significantly increased bone mass at both spine and hip trochanter and was generally well tolerated.