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1.
J Laryngol Otol ; 134(5): 440-446, 2020 May.
Article in English | MEDLINE | ID: mdl-32431257

ABSTRACT

BACKGROUND: Levamisole is an increasingly common cutting agent used with cocaine. Both cocaine and levamisole can have local and systemic effects on patients. METHODS: A retrospective case series was conducted of patients with a cocaine-induced midline destructive lesion or levamisole-induced vasculitis, who presented to a Dundee hospital or the practice of a single surgeon in Paisley, from April 2016 to April 2019. A literature review on the topic was also carried out. RESULTS: Nine patients from the two centres were identified. One patient appeared to have levamisole-induced vasculitis, with raised proteinase 3, perinuclear antineutrophil cytoplasmic antibodies positivity and arthralgia which improved on systemic steroids. The other eight patients had features of a cocaine-induced midline destructive lesion. CONCLUSION: As the use of cocaine increases, ENT surgeons will see more of the complications associated with it. This paper highlights some of the diagnostic issues and proposes a management strategy as a guide to this complex patient group. Often, multidisciplinary management is needed.


Subject(s)
Cocaine/adverse effects , Dopamine Uptake Inhibitors/adverse effects , Levamisole/adverse effects , Nicotinic Antagonists/adverse effects , Nose Diseases/chemically induced , Substance-Related Disorders/complications , Vasculitis/chemically induced , Adult , Cocaine-Related Disorders/complications , Female , Humans , Male , Middle Aged , Nasal Septal Perforation/chemically induced , Retrospective Studies
2.
J Laryngol Otol ; : 1-5, 2014 Mar 25.
Article in English | MEDLINE | ID: mdl-24666920

ABSTRACT

Objectives: To investigate rates of septorhinoplasty and rhinoplasty in Scotland between 2006 and 2010, and to establish the impact of government legislation. Methods: Data on the rates of rhinoplasty and septorhinoplasty were collected and analysed according to specialty, region and year. Results: In 2006, 754 septorhinoplasty and rhinoplasty cases were recorded (147 per million population), rising to 893 (171 per million population) in 2010. Mean annual rates per million population were 152 (87 per cent of procedures) in ENT, 13.9 (8 per cent) in plastic surgery and 8.7 (8 per cent) in oromaxillofacial surgery. After 2009, there was a 43 per cent reduction in the rhinoplasty rate (p < 0.0001), although the oromaxillofacial surgery rate increased by 68 per cent (p < 0.05). Over the same period, the septorhinoplasty rate increased in ENT (46 per cent, p < 0.0001), and declined in plastic surgery (24 per cent, p = 0.49) and oromaxillofacial surgery (45 per cent, p = 0.05). Overall, the rate for rhinoplasty plus septorhinoplasty only declined by 1 per cent. There was significant regional variation. Conclusion: Overall, septorhinoplasty rates have increased and rhinoplasty rates have decreased. There was only a 1 per cent decrease in the overall rate following the 2009 legislation. Practice differs between regions.

3.
Osteoporos Int ; 24(3): 907-15, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22836277

ABSTRACT

UNLABELLED: We examined the spinal distribution of the types of vertebral deformities and the associations of vertebral deformities and osteoarthritis with back pain in Japanese women. Midthoracic and upper lumbar vertebrae were more susceptible to deformity. Vertebral deformity and osteoarthritis were frequent and were associated with back pain. INTRODUCTION: Vertebral fractures due to osteoporosis and osteoarthritis are both common and significant health problems in aged people. However, little is known about the descriptive epidemiology of the individual deformity types and the relative clinical impact in women in Japan. METHODS: Lateral radiographs were obtained from 584 Japanese women ages 40 to 89 years old. Deformities were defined as vertebral heights of more than 3 standard deviations (SDs) below the normal mean. Osteoarthritis was defined as Kellgren-Lawrence (KL) grade 2 or higher. Information on upper or low back pain during the previous month was collected by questionnaire. We compared the spinal distribution of the three types of vertebral deformities (wedge, endplate, and crush) typical of fractures and examined the associations of number and type of vertebral deformities and osteoarthritis with back pain. RESULTS: Fifteen percent of women had at least one vertebral deformity and 74% had vertebral osteoarthritis. The prevalence of upper or low back pain was 30.1%. Deformities were most common in the midthoracic and upper lumbar regions and wedge was the frequent type, followed by endplate and crush. Multiple logistic regression analysis showed that the odds of back pain was 3.0 (95% CI 1.5-6.3) times higher for women with a single wedge deformity and 3.2 (95% CI 1.0--0.6) times higher for women with two or more wedge deformities, compared to women with no wedge deformity. Vertebral osteoarthritis was associated with back pain (OR 1.8, 95% CI 1.1-2.9), independent of other covariates including age and deformities. CONCLUSION: Our results in this group of Japanese women are similar to and consistent with results reported previously in other populations of Japanese and Caucasians.


Subject(s)
Back Pain/etiology , Osteoarthritis, Spine/complications , Osteoporotic Fractures/complications , Spinal Curvatures/complications , Spinal Fractures/complications , Adult , Age Distribution , Aged , Aged, 80 and over , Back Pain/epidemiology , Cross-Sectional Studies , Female , Humans , Japan/epidemiology , Lumbar Vertebrae/pathology , Middle Aged , Osteoarthritis, Spine/epidemiology , Osteoporosis, Postmenopausal/complications , Osteoporosis, Postmenopausal/epidemiology , Osteoporotic Fractures/epidemiology , Spinal Curvatures/epidemiology , Spinal Curvatures/pathology , Spinal Fractures/epidemiology , Thoracic Vertebrae/pathology
4.
Osteoporos Int ; 20(11): 1955-62, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19308301

ABSTRACT

UNLABELLED: Vitamin D status and its relationship to physical performance, falls, and fractures in 495 postmenopausal women of Japanese ancestry in Hawaii were investigated. The mean 25-hydroxyvitamin D (25-OHD) was 31.94 ng/mL. No significant association of 25-OHD was demonstrated with most outcomes, possibly due to higher 25-OHD levels in this population. INTRODUCTION: In this study, we investigated vitamin D status and its relationship to physical performance, muscle strength, falls, and fractures in postmenopausal Japanese females living in Hawaii. METHODS: Of 510 community-dwelling women who participated in the eighth examination of the Hawaii Osteoporosis Study, 495 were included in these analyses. Multivariate regression models were used to evaluate the relationship of 25-OHD (D(3) and total) to eight performance-based measurements, 12 activities of daily living (ADLs), and muscle strength (grip, triceps, and quadriceps). Logistic regression analyses were performed to evaluate the relationship of 25-OHD to falls, vertebral fractures, and non-vertebral fractures. RESULTS: The mean total 25-OHD was 31.94 +/- 9.46 ng/mL; 44% of subjects had values <30 ng/mL, while none had values <10-12 ng/mL. There was little evidence of seasonal variation. Among performance-based measures, ADLs, and strength tests, only quadriceps strength was significantly associated with total 25-OHD (p = 0.0063) and 25-OHD(3) (p = 0.0001). No significant association of 25-OHD was found with vertebral or non-vertebral fractures, or incidence of one or more falls. CONCLUSIONS: Lack of serum 25-OHD relationship with falls and fractures or most physical performance measures in this study may be related to the low prevalence of very low 25-OHD levels in this population.


Subject(s)
Accidental Falls/statistics & numerical data , Asian People/statistics & numerical data , Fractures, Bone/ethnology , Vitamin D/analogs & derivatives , Activities of Daily Living , Aged , Bone Density , Calcaneus/physiopathology , Female , Fractures, Bone/blood , Fractures, Bone/physiopathology , Frail Elderly , Hawaii/epidemiology , Humans , Japan/ethnology , Muscle Strength/physiology , Postmenopause/blood , Postmenopause/physiology , Seasons , Vitamin D/blood
5.
J Laryngol Otol ; 121(6): 584-7, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17040587

ABSTRACT

We set out to examine whether a multidisciplinary out-patient dysphagia referral triage service would shorten the duration of a patient's referral process and direct patients to the correct specialty. A review was carried out of patients referred with dysphagia before and after the introduction of a multidisciplinary out-patient dysphagia service, from February 2001 to April 2001 and from January 2002 to March 2002, inclusive. One hundred and eight patients were referred in total. The length of time until the first appointment was reduced from four to three weeks (median; range one to 23; p<0.001). The number of instrumental investigations was reduced, with a median of one instrumentation per patient under the new service, compared with two in those under the standard service (p<0.001). Attendance to hospital was also reduced, with 45 per cent of patients under the new service requiring only one appointment, compared with 13 per cent in those under the standard service (p<0.001). The multidisciplinary out-patient dysphagia service was associated with significant reductions in waiting times, in the number of instrumental investigations and in the duration of the patient's referral process.


Subject(s)
Ambulatory Care/organization & administration , Appointments and Schedules , Deglutition Disorders , Referral and Consultation/standards , Humans , Interdisciplinary Communication , Retrospective Studies
6.
Int J Clin Pract ; 60(11): 1394-400, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17026515

ABSTRACT

A number of antiresorptive agents reduce the risk of vertebral fractures, but few have shown consistent effects on hip and other non-spine fractures. Meta-analysis provides a more precise estimate than individual trials when results are consistent across pooled trials. Earlier meta-analyses summarised the results for vertebral and non-spine fractures. New data have emerged for hormone therapy (HT), alendronate (ALN), risedronate (RIS) and ibandronate (IBN). We surveyed recent reports of randomised, placebo-controlled trials with non-spine and/or hip fracture data, and used meta-analysis where appropriate to test for heterogeneity and derive pooled estimates. The magnitude of effect on hip fracture appears to be similar to that for non-spine fracture for each drug, but differs among drugs. Based on the current data, ALN reduces the risk of hip and non-spine fracture by 49-55%, HT by 25-36% and RIS by 26-27%. There is insufficient and/or inconsistent evidence of an effect on these fractures for IBN, calcitonin and raloxifene.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Fractures, Bone/prevention & control , Osteoporosis, Postmenopausal/drug therapy , Aged , Aged, 80 and over , Female , Fractures, Bone/etiology , Hip Fractures/etiology , Hip Fractures/prevention & control , Humans , Osteoporosis, Postmenopausal/complications , Randomized Controlled Trials as Topic , Risk Factors , Sensitivity and Specificity , Treatment Outcome
7.
QJM ; 97(1): 39-46, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14702510

ABSTRACT

BACKGROUND: Risk indices have been developed to identify women at risk of low bone mineral density (BMD) who should undergo BMD testing. AIM: To compare the performance of four risk indices in White ambulatory women in Belgium. DESIGN: Epidemiological cross-sectional study. METHODS: Records were analysed for 4035 postmenopausal White women without Paget's disease or advanced osteoarthritis, seen at an out-patient osteoporosis centre between January 1996 and September 1999. Osteoporosis risk index scores were compared to bone density T-scores. The ability of each risk index to identify women with low BMD (T-score < -2.0) or osteoporosis (T < -2.5) was evaluated. RESULTS: Using an Osteoporosis Self-Assessment Tool (OST) score <2 to recommend DXA referral, sensitivity ranged from 85% at the lumbar spine to 97% at the total hip to detect BMD T-scores of

Subject(s)
Health Status Indicators , Osteoporosis, Postmenopausal/diagnosis , Absorptiometry, Photon , Age Distribution , Aged , Aged, 80 and over , Bone Density , Epidemiologic Methods , Female , Femur Neck/physiopathology , Hip Joint/physiopathology , Humans , Lumbar Vertebrae/physiopathology , Middle Aged , Osteoporosis, Postmenopausal/etiology , Osteoporosis, Postmenopausal/physiopathology , Patient Selection
8.
Osteoporos Int ; 13(9): 723-30, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12195536

ABSTRACT

Vertebral fractures are a hallmark of postmenopausal osteoporosis and an important end point in trials of osteoporosis treatment, but the clinical significance of vertebral deformities remains uncertain. We examined the prevalence of vertebral deformity and associations of vertebral deformities and other characteristics with physical functioning among 584 Japanese women ages 40 to 89 years. Lateral spine radiographs were obtained and radiographic vertebral deformities were assessed by quantitative morphometry, defined as vertebral heights more than 3 SD below the normal mean. A self-administered questionnaire was used to survey participants about difficulty in performing selected basic and instrumental activities of daily living (ADL). Overall, 15% of women had at least one vertebral deformity, and 8% had 2 or more. The prevalence of vertebral deformities increased progressively with age. Half of women ages 80 and over had vertebral deformities. Impaired function was defined as difficulty performing 3 or more ADLs. After adjusting for age, the odds of impaired function were increased by 1.4 times (95% CI: 0.7, 2.9) in women with a single vertebral deformity, and 3.1 times (1.4, 6.8) in those with two or more deformities. Additional adjustment for number of painful joints, number of comorbidities, body mass index, and back pain did not materially alter these findings. In conclusion, women with multiple vertebral deformities had significantly greater impaired function. The association was independent of age, back pain and the number of painful joints, suggesting that deformities may impair function even when back pain is not present.


Subject(s)
Aging , Spinal Fractures/diagnostic imaging , Spine/abnormalities , Spine/diagnostic imaging , Activities of Daily Living , Adult , Aged , Aged, 80 and over , Back Pain/diagnostic imaging , Chi-Square Distribution , Cross-Sectional Studies , Female , Humans , Japan , Middle Aged , Prevalence , Radiography , Regression Analysis
9.
Calcif Tissue Int ; 69(4): 222-4, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11730255

ABSTRACT

Bone mineral density (BMD) is widely used in postmenopausal women to identify who should be given therapy for prevention and treatment of osteoporosis and to monitor the efficacy of treatment. There is still uncertainty about how to interpret BMD in men, and few prospective studies exist on the relationship between BMD and fracture risk. Men should be considered for measurement of BMD if they have suffered low trauma fractures, have prevalent vertebral deformities, have radiographic osteopenia, are over age 75, or have conditions that increase their risk for bone loss, such as hypogonadism, glucocorticoid use, or generally poor health. There is insufficient information to recommend a more widespread BMD screening. The World Health Organization has developed criteria for interpreting BMD which are widely used. Patients with BMD at least 2.5 SD below the young adult mean (T-score < -2.5) have osteoporosis, and those with BMD between 1 and -2.5 SD below the young adult mean (-2.5 < T-score < -1.0) have osteopenia. However, the BMD criteria that should be used to identify men in need of therapeutic intervention are still debated. Using male-specific hip BMD cutoffs, approximately 3-6% of U.S. men 50 years and older were estimated to have osteoporosis and 28-47% to have osteopenia. The corresponding figures in women were 13-18% with osteoporosis and 37-50% with osteopenia. Greater accumulation of skeletal mass during growth, slower rate of bone loss, and shorter life expectancy in men contribute to the lower prevalence of osteoporosis relative to women.


Subject(s)
Bone Density/physiology , Climacteric/physiology , Bone Diseases, Metabolic/complications , Bone Diseases, Metabolic/diagnosis , Bone Diseases, Metabolic/epidemiology , Female , Fractures, Spontaneous/diagnosis , Fractures, Spontaneous/epidemiology , Fractures, Spontaneous/etiology , Hip Fractures/epidemiology , Hip Fractures/etiology , Humans , Male , Osteoporosis, Postmenopausal/complications , Osteoporosis, Postmenopausal/diagnosis , Osteoporosis, Postmenopausal/epidemiology , Prevalence , Risk Factors , Sex Factors , Spinal Fractures/epidemiology , Spinal Fractures/etiology , United States/epidemiology
10.
BMC Geriatr ; 1: 3, 2001.
Article in English | MEDLINE | ID: mdl-11696243

ABSTRACT

BACKGROUND: Japanese (both in Japan and Hawaii) have a lower incidence of falls and of hip fracture than North American and European Caucasians, but the reasons for these differences are not clear. SUBJECTS AND METHODS: A cross-sectional study. We compared neuromuscular risk factors for falls using performance-based measures (chair stand time, usual and rapid walking speed, and grip strength) among 163 Japanese women in Japan, 681 Japanese-American women in Hawaii and 9403 Caucasian women in the United States aged 65 years and over. RESULTS: After adjusting for age, the Caucasian women required about 40% more time to complete 5 chair stands than either group of Japanese. Walking speed was about 10% slower among Caucasians than native Japanese, whereas Japanese-American women in Hawaii walked about 11% faster than native Japanese. Grip strength was greatest in Japan, which may reflect the rural farming district that this sample was drawn from. Additional adjustment for height, weight or body mass index increased the adjusted means of chair stand time and grip strength among Japanese, but the differences remained significant. CONCLUSIONS: Both native Japanese and Japanese-American women in Hawaii performed better than Caucasians on chair stand time and walking speed tests, and native Japanese had greater grip strength than Japanese in Hawaii and Caucasians. The biological implications of these differences in performance are uncertain, but may be useful in planning future comparisons between populations.

11.
Calcif Tissue Int ; 68(5): 291-6, 2001 May.
Article in English | MEDLINE | ID: mdl-11683536

ABSTRACT

We examined the associations of two biochemical markers of bone turnover with lifestyle factors in 340 postmenopausal women in Hawaii, ages 45-59 years, from the Early Postmenopausal Intervention Cohort. Physical activity, calcium supplement use, smoking and alcohol use in the prior 2 weeks were measured and examined as independent variables in multiple regression analyses with bone turnover markers as dependent variables, adjusted for weight, height, whole body bone mass, serum estradiol, years since menopause, and ethnicity. Calcium supplement and alcohol use were significantly associated with reduced levels of urinary type I collagen cross-linked N-telopeptides (NTX). The mean NTX level was 12% lower among women using > or = 250 mg of calcium supplements per day as compared with other women, and 20% lower among alcohol users compared with nonusers. Both calcium supplement use and alcohol intake were associated with lower mean serum osteocalcin (a marker of bone formation) and NTX z-scores. By contrast, smoking was associated with lower osteocalcin levels, without any effect on NTX. The osteocalcin level was 12% lower among smokers compared with nonsmokers. In addition, the z-score difference between NTX and osteocalcin was significantly associated with smoking, with a shift towards more NTX than osteocalcin. Physical activity was not significantly associated with either of the markers. These findings suggest that biochemical markers may help to identify lifestyle factors that affect bone, and provide estimates of the relative magnitude of these effects on bone formation and resorption, independent of each other.


Subject(s)
Bone Remodeling/physiology , Life Style , Osteoporosis, Postmenopausal/metabolism , Postmenopause/metabolism , Alcohol Drinking , Biomarkers , Calcium , Cohort Studies , Collagen/urine , Collagen Type I , Dietary Supplements , Female , Hawaii/epidemiology , Humans , Middle Aged , Osteocalcin/blood , Osteoporosis, Postmenopausal/epidemiology , Peptides/urine , Physical Fitness , Risk Factors , Smoking
12.
Calcif Tissue Int ; 69(1): 20-4, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11685429

ABSTRACT

The aging process is associated with an increasing prevalence of osteoporosis and aortic calcification, but it is uncertain if these two conditions are interrelated. We examined the relationship between bone mineral density (BMD) and evidence of aortic calcification on spinal radiographs among 524 Japanese-American women living in Hawaii. The prevalence of aortic calcification increased with age from less than 10% below age 55 to essentially all women over age 75. Unadjusted BMD was significantly lower among women with aortic calcification at all measured sites (distal and proximal radius and calcaneus). However, the differences in BMD between women with and without calcification were diminished and no longer significant after adjustment for age. Aortic calcification was positively associated with body mass index (BMI), systolic blood pressure, diabetes, current smoking, and thiazide use, but negatively associated with physical activity index. Multivariate logistic regression analysis showed that age, systolic blood pressure, physical activity index (protective), and current smoking (common etiological factors for aortic calcification) were independently associated with aortic calcification, whereas BMD (mean Z-score) was not. We conclude that there is little evidence to support a direct relationship between osteoporosis (low BMD) and aortic calcification. Osteoporosis and aortic calcification appear to be independent processes that occur as women age. However, potential confounding factors may be involved, and prospective studies are needed to investigate this issue further.


Subject(s)
Aortic Diseases/etiology , Bone Density , Calcinosis/etiology , Osteoporosis, Postmenopausal/complications , Adult , Aged , Aging/physiology , Aortic Diseases/diagnostic imaging , Aortic Diseases/metabolism , Blood Pressure , Body Mass Index , Calcaneus/diagnostic imaging , Calcaneus/metabolism , Calcinosis/ethnology , Calcinosis/metabolism , Female , Humans , Logistic Models , Middle Aged , Odds Ratio , Osteoporosis, Postmenopausal/diagnostic imaging , Osteoporosis, Postmenopausal/metabolism , Radiography , Radius/diagnostic imaging , Radius/metabolism
13.
Aging (Milano) ; 12(5): 356-9, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11126521

ABSTRACT

Age-specific hip fracture incidence has been increasing in some parts of the world. The incidence of hip fractures among Japanese on the island of Oahu, Hawaii in 1979-1981 was approximately half that of Caucasians in North America, but similar to the incidence in Japan. We surveyed the incidence on Oahu again in 1991-1995 for all races to compare the incidence among Japanese to the earlier rates, and to other populations, including Caucasians on Oahu. The incidence of hip fracture among Japanese in Hawaii between 1991-1995 had not changed appreciably (compared to 1979-1981), and was similar to that among Caucasians on Oahu. The incidence among Hawaii Japanese and Caucasians was similar to, or lower than Japan overall, and much lower (one-third to one-half) than that reported for Caucasians in North America and Northern Europe, suggesting that the prevalence of certain risk factors may be lower in Hawaii. These findings confirm other studies suggesting that nongenetic factors may be responsible for much of the observed differences in hip fracture incidence between countries, and between races.


Subject(s)
Ethnicity/statistics & numerical data , Hip Fractures/epidemiology , White People/statistics & numerical data , Age Distribution , Aged , Aged, 80 and over , Female , Hawaii/epidemiology , Humans , Incidence , Japan/epidemiology , Male , Middle Aged , Sex Distribution
14.
Mayo Clin Proc ; 75(9): 888-96, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10994823

ABSTRACT

OBJECTIVE: To evaluate the ability of self-reported risk factors to identify postmenopausal women likely to have extant vertebral fractures because approximately two thirds of women with radiographic evidence of vertebral fracture are unaware of the fracture. PATIENTS AND METHODS: Questionnaire and spinal radiographic data were collected from postmenopausal women with a femoral neck bone mineral density T score of -1.6 or lower during screening for the Fracture Intervention Trial. Logistic regression was used to identify risk factors for extant vertebral fractures and to derive a final multivariable model. RESULTS: Almost two thirds of 25,816 women 55 years and older met the bone density criterion, and 21% of those had an extant vertebral fracture. The final model consisted of 5 self-reported items: history of vertebral fracture, history of nonvertebral fracture, age, height loss, and diagnosis of osteoporosis. These were combined to yield a Prevalent Vertebral Fracture Index (PVFI). The prevalence of women with vertebral fracture varied from 3.8% to 62.3% over the range PVFI of 0 to greater than 5. Among the 13,051 women screened with spinal radiographs, a PVFI of 4 or greater identified 65.5% of women with vertebral fractures (sensitivity), with a specificity of 68.6%. Excluding 881 women who reported prior vertebral fractures reduced the sensitivity to 53.6 % and increased the specificity to 70.7% but did not alter the fracture prevalence at PVFI values less than 6. CONCLUSION: In this population, 5 simple questions identified women who were likely to have undiagnosed vertebral fractures. Further research is needed to determine the validity of this index in other populations, including women without low bone mineral density.


Subject(s)
Mass Screening/methods , Medical History Taking/methods , Osteoporosis, Postmenopausal/complications , Spinal Fractures/diagnosis , Spinal Fractures/etiology , Surveys and Questionnaires/standards , Age Distribution , Aged , Aged, 80 and over , Body Height , Bone Density , Female , Femur Neck/diagnostic imaging , Humans , Logistic Models , Middle Aged , Multivariate Analysis , Prevalence , Radiography , Reproducibility of Results , Risk Factors , Sensitivity and Specificity , Spinal Fractures/epidemiology , United States/epidemiology
15.
J Clin Endocrinol Metab ; 85(9): 3109-15, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10999794

ABSTRACT

We report here the second 2-yr extension of a clinical trial among postmenopausal women; 235 women continued blinded treatment with 5 or 10 mg alendronate daily, and 115 women who had been treated with alendronate for 5 yr were switched to blinded placebo. Continuous treatment with alendronate (10 mg daily) for 7 yr increased lumbar spine bone mineral density (BMD) by 11.4% compared to baseline. After the initial 18 months, each additional year of treatment through yr 7 increased spine BMD by 0.8% for the 10-mg dose and 0.6% for the 5-mg dose, with significant increases during yr 6-7. Previously reported increases in BMD at other skeletal sites and decreases in biochemical markers of bone turnover remained stable during yr 6-7. Among women previously taking alendronate for 5 yr who were switched to placebo, there was no significant decline in BMD at the spine or hip, whereas small, but significant, decreases in BMD at the forearm and total body and small increases in biochemical markers were observed. The safety and tolerability profiles were similar to those of placebo. This is the largest published long-term study of antiresorptive therapy. Our findings indicate that long-term alendronate treatment is well tolerated and effective for 7 yr. Increases in spinal BMD continue for at least 7 yr, and other skeletal benefits are maintained. Discontinuation does not lead to accelerated bone loss, but continuous treatment yields better skeletal benefits than shorter treatment.


Subject(s)
Alendronate/therapeutic use , Bone Density/drug effects , Osteoporosis, Postmenopausal/drug therapy , Absorptiometry, Photon , Aged , Alendronate/adverse effects , Bone and Bones/diagnostic imaging , Double-Blind Method , Female , Humans , Middle Aged , Osteoporosis, Postmenopausal/pathology , Time Factors
16.
Calcif Tissue Int ; 67(2): 106-10, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10920213

ABSTRACT

Fracture risk is influenced by both bone strength and by falls. Measures of physical function and performance are predictors of falls. However, the interrelationships among bone mineral density (BMD), regular physical activity, and measures of physical performance are not well known. We studied 447 community-dwelling Japanese people aged 40 years and over (96 men and 351 women) to examine the association of calcaneus BMD with measures of physical performance (grip strength, walking speed, chair stand, and functional reach) and regular physical activity. Calcaneus BMD decreased with age by approximately 25% in men and 42% in women. Measures of physical performance decreased with age by approximately 30% in both genders, however, performance on the chair stand test declined by approximately 60%. There were only minimal differences in performance measures and calcaneus BMD between people with and those without regular physical activity in both genders, and most differences were not significant. However, there were significant BMD increases of 3-6% per standard deviation (SD) increase in all performance measures for women and a 7% increase in BMD per SD increase in grip strength for men, after adjusting for age. These associations remained after additional adjustment for body mass index and regular physical activity. These findings suggest that bone density and physical function decline markedly in both men and women with age, and that low BMD and poor function tend to occur together, which would increase fracture risk more than either risk factor alone.


Subject(s)
Bone Density , Calcaneus/anatomy & histology , Absorptiometry, Photon , Age Factors , Calcaneus/chemistry , Female , Humans , Japan , Male , Middle Aged , Physical Fitness
17.
J Bone Miner Res ; 15(4): 721-39, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10780864

ABSTRACT

Numerous studies have reported increased risks of hip, spine, and other fractures among people who had previous clinically diagnosed fractures, or who have radiographic evidence of vertebral fractures. However, there is some variability in the magnitudes of associations among studies. We summarized the literature and performed a statistical synthesis of the risk of future fracture, given a history of prior fracture. The strongest associations were observed between prior and subsequent vertebral fractures; women with preexisting vertebral fractures (identified at baseline by vertebral morphometry) had approximately 4 times greater risk of subsequent vertebral fractures than those without prior fractures. This risk increases with the number of prior vertebral fractures. Most studies reported relative risks of approximately 2 for other combinations of prior and future fracture sites (hip, spine, wrist, or any site). The confidence profile method was used to derive a single pooled estimate from the studies that provided sufficient data for other combinations of prior and subsequent fracture sites. Studies of peri- and postmenopausal women with prior fractures had 2.0 (95 % CI = 1.8, 2.1) times the risk of subsequent fracture compared with women without prior fractures. For other studies (including men and women of all ages), the risk was increased by 2.2 (1.9, 2.6) times. We conclude that history of prior fracture at any site is an important risk factor for future fractures. Patients with a history of prior fracture, therefore, should receive further evaluation for osteoporosis and fracture risk.


Subject(s)
Fractures, Bone , Aged , Case-Control Studies , Cross-Sectional Studies , Female , Fractures, Bone/epidemiology , Humans , Male , Mathematical Computing , Medical History Taking , Middle Aged , Prospective Studies , Risk Factors , Spinal Fractures
18.
Clin Ther ; 22(1): 15-28, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10688387

ABSTRACT

OBJECTIVE: This paper describes the rationale and supporting data for once-weekly dosing of alendronate. BACKGROUND: Alendronate sodium, a bisphosphonate that potently inhibits bone resorption, has been shown to increase bone mass and substantially reduce the incidence of osteoporotic fractures, including fractures of the hip. The standard regimen of daily administration has generally been well tolerated. However, weekly administration may provide greater convenience to patients without compromising efficacy or tolerability. The pharmacokinetics of alendronate and bone remodeling theory predict similar efficacy for weekly and daily administration if the cumulative dose is the same. Bone resorption in individual remodeling units normally proceeds for approximately 2 weeks; alendronate inhibits the rate and extent of resorption. Because the half-life of residence on bone surfaces is several weeks, weekly administration of alendronate should inhibit bone resorption to an overall extent similar to that of daily dosing, thereby producing similar effects on bone mass and strength. Animal studies demonstrate that both weekly and daily parenteral administration of alendronate effectively increase bone mass and strength, but confirmation of efficacy is needed for weekly oral dosing in humans. Although daily bisphosphonates (alendronate and risedronate) elicited esophageal irritation in a canine model of gastroesophageal reflux, weekly dosing with alendronate at a higher unit dose did not. Thus, the lower frequency of weekly dosing with a higher unit dose may actually reduce the risk of upper gastrointestinal irritation compared with daily administration of a lower dose. CONCLUSIONS: Current safety and efficacy data justify further investigation of once-weekly dosing of alendronate. Two positive-control, double-blind, randomized trials of osteoporosis treatment and prevention are currently being performed to assess the comparability of weekly, biweekly, and daily dosing of alendronate with regard to effects on bone density, safety, and tolerability.


Subject(s)
Alendronate/administration & dosage , Alendronate/therapeutic use , Bone Resorption/drug therapy , Animals , Bone Remodeling/drug effects , Dogs , Humans
19.
Osteoporos Int ; 11(1): 76-82, 2000.
Article in English | MEDLINE | ID: mdl-10663362

ABSTRACT

The aim of this study was to assess the ability of serum bone-specific alkaline phosphatase (bone ALP), creatinine-corrected urinary collagen crosslinks (CTx) and calcaneus bone mineral density (BMD) to identify postmenopausal women who have an increased risk of osteoporotic fractures. Calcaneus BMD and biochemical markers of bone turnover (serum bone ALP and urinary CTx) were measured in 512 community-dwelling postmenopausal women (mean age at baseline 69 years) participating in the Hawaii Osteoporosis Study. New spine and nonspine fractures subsequent to the BMD and biochemical bone markers measurements were recorded over an average of 2.7 years. Lateral spinal radiographs were used to identify spine fractures. Nonspine fractures were identified by self-report at the time of each examination. During the 2.7-year follow-up, at least one osteoporotic fracture occurred in 55 (10.7%) of the 512 women. Mean baseline serum bone ALP and urinary CTx were significantly higher among women who experienced an osteoporotic fracture compared with those women who did not fracture. In separate age-adjusted logistic regression models, serum bone ALP, urinary CTx and calcaneus BMD were each significantly associated with new fractures (odds ratios of 1.53, 1.54 and 1.61 per SD, respectively). Multiple variable logistic regression analysis identified BMD and serum bone ALP as significant predictors of fracture (p = 0.002 and 0.017, respectively). The results from this investigation indicate that increased bone turnover is significantly associated with an increased risk of osteoporotic fracture in postmenopausal women. This association is similar in magnitude and independent of that observed for BMD.


Subject(s)
Alkaline Phosphatase/metabolism , Bone Density/physiology , Calcaneus/enzymology , Creatinine/metabolism , Fractures, Bone/diagnosis , Aged , Aged, 80 and over , Biomarkers , Female , Fractures, Bone/enzymology , Fractures, Spontaneous/diagnosis , Fractures, Spontaneous/enzymology , Humans , Middle Aged , Osteoporosis/enzymology , Osteoporosis/physiopathology , Postmenopause , Prospective Studies , Risk Factors
20.
J Clin Densitom ; 3(4): 365-71, 2000.
Article in English | MEDLINE | ID: mdl-11175917

ABSTRACT

We studied the associations between body composition and biochemical markers of bone formation and resorption among 1600 postmenopausal women, ages 45-59. Multiple regression analyses were performed to examine the independent associations of fat mass, muscle strength (quadriceps strength), height, and whole body bone mineral content (BMC) with biochemical markers of bone formation (serum osteocalcin) and resorption (urinary type I collagen crosslinked N-telopeptides [NTX]). Per interquartile range (IQR) (the difference between 75th and 25th percentiles) increase in fat mass and whole body BMC, the mean levels of osteocalcin decreased by 3% and 13%, respectively; NTX decreased by 5 and 21%. Fat mass and whole-body BMC were also significantly associated with decreases in the average of osteocalcin and NTX Z-scores. By contrast, the mean levels of serum osteocalcin increased by 2 and 11%, respectively, per IQR increase in muscle strength and height; NTX increased by 4 (not significant) and 14%, respectively. Both muscle strength and height were significantly associated with increases in the average Z-scores. These exploratory analyses suggest that fat mass and whole-body BMC were associated with decreased bone turnover, while muscle strength and height were associated with increased bone turnover.


Subject(s)
Body Composition , Bone Remodeling/physiology , Osteogenesis , Postmenopause/physiology , Adipose Tissue/physiology , Bone Resorption/physiopathology , Female , Humans , Immunoradiometric Assay , Middle Aged , Muscle, Skeletal/physiology , Osteocalcin/blood , Randomized Controlled Trials as Topic , Regression Analysis
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