A Randomized Trial of Sodium Fluoride (60 mg) ± Estrogen in Postmenopausal Osteoporotic Vertebral Fractures: Increased Vertebral Fractures and Peripheral Bone Loss with Sodium Fluoride; Concurrent Estrogen Prevents Peripheral Loss, But Not Vertebral Fractures

Postmenopausal Caucasian women aged less than 80 years (n= 99) with one or more atraumatic vertebral fracture and no hip fractures, were treated by cyclical administration of enteric coated sodium fluoride (NaF) or no NaF for 27 months, with precautions to prevent excessive stimulation of bone turnover. In the first study 65 women, unexposed to estrogen (–E study), age 70.8 ± 0.8 years (mean ± SEM) were all treated with calcium (Ca) 1.0–1.2 g daily and ergocalciferol (D) 0.25 mg per 25 kg once weekly and were randomly assigned to cyclical NaF (6 months on, 3 months off, initial dose 60 mg/day; group F CaD, n= 34) or no NaF (group CaD, n= 31). In the second study 34 patients, age 65.5 ± 1.2 years, on hormone replacement therapy (E) at baseline, had this standardized, and were all treated with Ca and D and similarly randomized (FE CaD, n= 17; E CaD, n= 17) (+E study). The patients were stratified according to E status and subsequently assigned randomly to ± NaF. Seventy-five patients completed the trial. Both groups treated with NaF showed an increase in lumbar spinal density (by DXA) above baseline by 27 months: FE CaD + 16.2% and F CaD +9.3% (both p= 0.0001). In neither group CaD nor E CaD did lumbar spinal density increase. Peripheral bone loss occurred at most sites in the F CaD group at 27 months: tibia/fibula shaft –7.3% (p= 0.005); femoral shaft –7.1% (p= 0.004); distal forearm –4.0% (p = 0.004); total hip –4.1% (p = 0.003); and femoral neck –3.5% (p= 0.006). No significant loss occurred in group FE CaD. Differences between the two NaF groups were greatest at the total hip at 27 months but were not significant [p<0.05; in view of the multiple bone mineral density (BMD) sites, an alpha of 0.01 was employed to denote significance in BMD changes throughout this paper]. Using Cox’s proportional hazards model, in the –E study there were significantly more patients with first fresh vertebral fractures in those treated with NaF than in those not so treated (RR = 24.2, p= 0.008, 95% CI 2.3–255). Patients developing first fresh fractures in the first 9 months were markedly different between groups: –23% of F CaD, 0 of CaD, 29% of FE CaD and 0 of E CaD. The incidence of incomplete (stress) fractures was similar in the two NaF-treated groups. Complete nonvertebral fractures did not occur in the two +E groups; there were no differences between groups F CaD and CaD. Baseline BMD (spine and femoral neck) was related to incident vertebral fractures in the control groups (no NaF), but not in the two NaF groups. Our results and a literature review indicate that fluoride salts, if used, should be at low dosage, with pretreatment and co-treatment with a bone resorption inhibitor. Received: 22 August 2000 / Accepted: 23 July 2001     

Vertebral Fractures Predict Subsequent Fractures

This population-based study documents an increase in most types of fractures following the occurrence of a clinically recognized vertebral fracture among 820 Rochester, Minnesota, residents. During 4349 person-years of follow-up, 896 new fractures were observed. Relative to incidence rates in the community, there was a 2.8-fold increase in the risk of any fracture, which was greater in men (standardized incidence ratio (SIR), 4.2; 95% CI, 3.2–5.3) than women (SIR, 2.7; 95% CI, 2.4–3.0). The estimated cumulative incidence of any fracture after 10 years was 70%. The greatest increase in risk was for subsequent fractures of the axial skeleton, in particular a 12.6-fold increase (95% CI, 11–14) in additional vertebral fractures. There was a lesser increase in most limb fractures, including a 2.3-fold increase (95% CI, 1.8–2.9) in hip fractures and a 1.6-fold increase (95% CI, 1.01–2.4) in distal forearm fractures. There was a slightly greater association with distal forearm fractures among those whose first vertebral fracture occurred before age 70 years but a similar relationship with hip fractures, including cervical and intertrochanteric hip fractures separately, regardless of age at the initial vertebral fracture. There was also an equivalent increase in subsequent fracture risk whether the initial vertebral fracture was attributed to severe or moderate trauma. These data show that vertebral fractures represent an important risk factor for fractures in general, not just those of the spine and hip. Received: 2 September 1998 / Accepted: 9 February 1999     

Prevalent Vertebral Deformity Predicts Incident Hip though not distal Forearm Fracture: Results from the European Prospective Osteoporosis Study

The presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40 348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1–9.4) and a weak predictor of ‘other’ limb fractures (RR = 1.6; 95% CI 1.1–2.4), though not distal forearm fracture (RR = 1.0; 95% CI 0.6–1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0–17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and ‘other’ limb fractures; however, they do not predict distal forearm fractures. Received: 23 February 2000 / Accepted: 11 August 2000     

A Meta-analysis of Etidronate for the Treatment of Postmenopausal Osteoporosis

The aim of the study was to review the effect of etidronate on bone density and fractures in postmenopausal women. We searched MEDLINE from 1966 to 1998, examined citations of relevant articles, and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies, primary authors, and pharmaceutical industry sources for unpublished data. We included 13 trials that randomized women to etidronate or an alternative (placebo or calcium and/or vitamin D) and measured bone density for at least 1 year. For each trial, three independent reviewers assessed the methodologic quality and abstracted data. The data suggested a reduction in vertebral fractures with a pooled relative risk of 0.63 (95% CI 0.44 to 0.92). There was no effect on nonvertebral fractures (relative risk 0.99, (95% CI 0.69 to 1.42). Etidronate, relative to control, increased bone density after 1–3 years of treatment in the lumbar spine by 4.06% (95% CI 3.12 to 5.00), in the femoral neck by 2.35% (95% CI 1.66 to 3.04) and in the total body by 0.97% (95% CI 0.39 to 1.55). Effects were larger at 4 years, though the number of patients followed much smaller. Etidronate increases bone density in the lumbar spine and femoral neck for up to 4 years. The pooled estimates of fracture reduction with etidronate suggest a reduction in vertebral fractures, but no effect on nonvertebral fractures. Received: 25 February 2000 / Accepted: 8 August 2000     

The Health Consequences of Vertebral Deformity in Elderly Chinese Men and Women

The following health consequences of vertebral deformity in Hong Kong elderly Chinese men and women were studied: the prevalence of back pain, disability due to back pain, and low morale. Lateral X-ray films were taken of the thoracic and lumbar spine of 796 community-dwelling Chinese subjects (396 men, 400 women) (aged 70–79). Subjects with one or more definitely deformed vertebra (reduction in vertebral height 3 SD or more below the mean) were classified as definite cases, those with one or more mildly deformed vertebra (reduction in vertebral height 2–2.99 SD below the mean) as mild cases, and the rest as controls. The prevalence and consequences of back pain were measured by a standardized questionnaire, and morale was measured by the Geriatric Morale Score. The relative risk (RR) and 95% confidence interval (CI) of having back pain and being depressed were calculated by logistic regression. Classifications included 16% of men and 30% of women as definite cases, 37% of men and 35% of women as mild cases, and 47% of men and 35% of women as controls. The relative risk (RR) of back pain was 2.3 (95% CI 1.4–3.9) (P < 0.05) in women with definite deformity and 1.5 (95% CI 0.9–2.5) (P > 0.05) in women with mild deformity, as compared with controls. Sixty-four percent of all men had back pain. This prevalence was much higher than figures obtained in a previous survey on low back pain. The prevalence of back pain did not differ by deformity status, but more men with vertebral deformity were on analgesic. There was no significant association between disability due to back pain and vertebral deformity in women. The RR for having a low morale score (of 5 and below) was 2.3 (95% CI 1.3–4.1) (P < 0.05) in women with mild deformity; men with vertebral deformity did not have a low morale. It was concluded that vertebral deformity was associated with significant back pain and psychological morbidity in elderly Chinese women. Although men with vertebral deformity did not report more back pain, more were on analgesics than controls. Received: 2 July 1997 / Accepted: 8 January 1998     

Metacarpal Morphometry Using a Semi-automated Technique in the Assessment of Osteoporosis and Vertebral Fracture Risk

Metacarpal morphometry represents a potentially cheap and widely available non-invasive assessment of skeletal status. In two cross-sectional studies, we compared the performance characteristics of a semi-automated technique (the Teijin Bonalyzer) with an in-house manual measurement, and with measures of skeletal strength at other sites. The metacarpal cortical index (mCI) was measured on hand radiographs of 178 osteoporotic women using both the Teijin Bonalyzer and a digitizing tablet. Measurements on the latter were consistently lower than with the Bonalyzer except for mCI (0.443 ± 0.080 vs 0.364 ± 0.060, p<0.001), although correlation coefficients between these two methods were highly significant (r= 0.62–0.83, p<0.001). The reproducibility errors of metacarpal bone mineral density (mBMD) were constant (1.1–1.2%) whilst those for mCI showed a marked operator-dependency (2.0–7.9%). In 379 elderly community-dwelling women, Bonalyzer mCI and mBMD showed a significant decline with age (r=−0.30 and −0.27 respectively, p<0.05). Both mCI and mBMD correlated significantly with forearm BMD (r= 0.50 and 0.57 respectively, p<0.001) and hip BMD (r= 0.48 and 0.53 respectively, p<0.001). After adjustment for age and weight, hip BMD demonstrated the best discrimination for prevalent vertebral fractures as judged by the gradient of risk for a 1 SD decrease in measurement (odds ratio (OR) 2.17, 95% CI 1.56–3.01). Similar but smaller gradients of risk were shown by Bonalyzer mCI (OR 1.32, 95% CI 1.00–1.75), mBMD (OR 1.35, 95% CI 1.02–1.78) and forearm BMD (OR 1.39, 95% CI 1.08–1.80). MCI, and in particular mBMD, may be useful assessments of bone mass and fracture risk. In our study, it is comparable to peripheral assessment of skeletal status by forearm densitometry. Received: 22 February 2000 / Accepted: 6 June 2000     

The Tromsø Study: Registration of Fractures, How Good are Self-reports, a Computerized Radiographic Register and a Discharge Register?

In order to compare different methods of fracture registration, we sought all nonvertebral fractures suffered during 8 years (1988–95) among 21 441 persons invited to a survey in 1979/80. We registered a total of 54 hip fracture cases through three separate sources (self-report, computer linkage to the local radiographic archives, discharge register), whereas forearm fractures (a total of 291 cases) were registered through two separate sources (self-report, computer linkage to the radiographic archives). The registration of fractures at other sites (a total of 1321 cases) were from one source (computer linkage to the local radiographic archives), and we have compared three ways of obtaining data from this single source (no ascertainment, ascertainment of records coded as fracture, ascertainment of all records). Ninety-three percent of all hip fractures and 97% of all wrist fractures in the entire study population were found by computer linkage to the radiographic archives, whereas the discharge register detected 87% of all the hip fractures. Computer linkage with ascertainment gave no overreporting of fractures. Among the 11 626 persons who answered a follow-up questionnaire in 1994/95, 97% (CI 84–100%) of all hip fractures and 72% (CI 66–78%) of all wrist fractures were self-reported. We conclude that a computerized search of radiographic archives is a viable method of fracture registration. Received: 8 February 1999 / Accepted: 11 June 2001     

Bone Mineral Density and Bone Size in Men With Primary Osteoporosis and Vertebral Fractures

The bone mineral density (BMD) at the lumbar spine, proximal femur, and total skeleton was evaluated in 38 men with primary osteoporosis and vertebral fractures. BMD of the patients was significantly reduced over all skeletal areas compared with controls. The Z-score of the lumbar spine (−2.8 ± 0.9) was less than that of the other areas (P < 0.001) except the legs (−2.5 ± 1.1) (p.n.s.) showing that bone loss had a tendency to be greater over the axial skeleton. Vertebral dimensions compared with age-matched controls were as follows: projected L2–L4 area (cm 2): 45.7 ± 5.6 versus 53.7 ± 3.6 (P < 0.001); vertebral width (cm): 4.37 ± 0.44 versus 4.90 ± 0.36 (P < 0.001). Serum biochemical parameters and testosterone levels were similar between osteoporotic and control men. We conclude that men with vertebral osteoporotic fractures have reduced vertebral BMD and vertebral dimensions compared with age-matched controls. Thus, these findings indicate that the achievement of a reduced bone size at the end of the growth period or a failure of periosteal increase during adult life is likely to contribute to the pathogenesis of the vertebral fractures observed in older men. Received: 31 January 1997 / Accepted: 2 July 1997     

Differences in Risk Factor Patterns Between Cervical and Trochanteric Hip Fractures

The two types of hip fracture – cervical and trochanteric femoral fractures – are generally considered together in etiologic studies. However, women with a trochanteric fracture may be more osteoporotic than those with cervical hip fractures, and have higher post-fracture mortality. To explore differences in risk factor patterns between the two types of hip fracture we used data from a large population-based case–control study in Swedish women, 50–81 years of age. Data were collected by questionnaire, to which more than 80% of subjects responded. Of the cases included, 811 had had a cervical fracture and 483 a trochanteric fracture during the study period; these cases were compared with 3312 randomly selected controls. Height and hormonal factors appeared to affect the risk of the two types of hip fracture differently. For every 5 cm of current height, women with a cervical fracture had an adjusted odds ratio (OR) of 1.23 (95% CI 1.15–1.32) compared with an OR of 1.06 (95% CI 0.97–1.15) for women with trochanteric fractures. Later menopausal age was protective for trochanteric fractures (OR 0.95, 95% CI 0.91–0.99 per 2 years) but no such association was found for cervical fractures. Compared with never smokers, current smokers had an OR of 1.48 (95% CI 1.12–1.95) for trochanteric fractures and 1.22 (95% CI 0.98–1.52) for cervical fractures. Current hormone replacement therapy was similarly protective for both fracture types, but former use substantially reduced risk only for trochanteric fractures: OR 0.55 (95% CI 0.33–0.92) compared with 1.00 (95% CI 0.71–1.39) for cervical fractures. These risk factor patterns suggest etiologic differences between the fracture types which have to be considered when planning preventive interventions. Received: 22 March 1999 / Accepted: 28 May 1999     

Risk Factors for Perimenopausal Fractures: A Prospective Study

This prospective study was aimed at determining the risk factors for the development of fractures in perimenopausal women. The study group (n= 3068) was comprised of a stratified population sample of women aged between 47 and 56 years. During the follow-up period of 3.6 years, 257 (8.4%) of the women sustained a total of 295 fractures. After adjustment for covariates, the relative risk (RR) of sustaining a fracture was found to be 1.4 [95% confidence interval (CI) 1.2–1.6] for a 1 standard deviation (SD) decrease in the spinal and femoral neck bone mineral density (BMD). Women with a previous fracture history were found to have an increased risk of fracture [RR 1.7 (95% CI 1.3–2.2)] and those reporting three or more chronic illnesses exhibited a RR of 1.4 (95% CI 1.0–1.9). Women not using hormone replacement therapy (HRT) had a RR of 1.5 (95% CI 1.1–2.2) for all fracture types. When osteoporotic fractures (vertebral, hip, proximal humerus and wrist fractures; n= 98) were used as an endpoint, the independent risk factors were found to be a low BMD (RR for a 1 SD decrease in both spinal and femoral neck BMD was 1.6, 95% CI 1.3–2.0), a previous fracture history (RR 1.9, 95% CI 1.3–2.9) and nonuse of HRT (RR 2.2, 95% CI 1.3–4.0). The independent risk factors for all other fractures (n = 158) were a low BMD (RR for a 1 SD decrease in the spinal BMD was 1.4, 95% CI 1.2–1.6 and in the femoral neck BMD was 1.3, 95% CI 1.1–1.5), a previous fracture history (RR 1.6, 95% CI 1.1–2.2), smoking (RR 1.8, 95% CI 1.1–2.7) and having had three or more chronic illnesses (RR 1.6, 95% CI 1.1–2.2). Weight, height, age, menopausal status, maternal hip fracture, use of alcohol, coffee consumption or dietary calcium intake were not independently associated with the development of any particular type of fracture. We conclude that the independent risk factors for perimenopausal fractures are a low bone density, previous fracture history, nonuse of HRT, having had three or more chronic illnesses and smoking, the gradient of risk being similar for spinal and femoral neck BMD measurements in the perimenopausal population. The risk factors are slightly different for perimenopausal osteoporotic than for other types of fractures. Received: 6 April 1999 / Accepted: 18 August 1999     

Proximal Femur Geometry To Detect and Distinguish Femoral Neck Fractures from Trochanteric Fractures in Postmenopausal Women

Some proximal femur geometry (PFG) parameters, measured by dual-energy X-ray absorptiometry (DXA), have been reported to discriminate subjects with hip fracture. Relatively few studies have tested their ability to discriminate femoral neck fractures from those of the trochanter. To this end we performed a cross-sectional study in a population of 547 menopausal women over 69 years of age with femoral neck fractures (n= 88), trochanteric fractures (n= 93) or controls (n= 366). Hip axis length (HAL), neck–shaft angle (NSA), femoral neck diameter (FND) and femoral shaft diameter (FSD) were measured by DXA, as well as the bone mineral density (BMD) of the nonfractured hip at the femoral neck, trochanter and Ward’s triangle. In fractured subjects, BMD was lower at each measurement site. HAL was longer and NSA wider in those with femoral neck fractures. With logistic regression the age-adjusted odds ratio (OR) for a 1 standard deviation (SD) decrease in BMD was significantly associated at each measurement site with femoral neck fracture (femoral neck BMD: OR 1.9, 95% confidence interval (95% CI): 1.4–2.5; trochanter BMD: OR 1.6, 95% CI 1.2–2.0; Ward’s triangle BMD: OR 1.7, 95% CI 1.3–2.2) and trochanteric fracture (femoral neck BMD: OR 2.6, 95% CI 1.9–3.6; trochanter BMD: OR 3.0, 95% CI 2.2–4.1; Ward’s triangle BMD: OR 1.8, 95% CI 1.4–2.3). Age-adjusted OR for 1 SD increases in NSA (OR 2.2, 95% CI 1.7–2.8) and HAL (OR 1.3, 95% CI 1.1–1.6) was significantly associated with the fracture risk only for femoral neck fracture. In the best predictive model the strongest predictors were site-matched BMD for both fracture types and NSA for neck fracture. Trochanteric BMD had the greatest area (0.78, standard error (SE) 0.02) under the receiver operating characteristic curve in trochanteric fractures, whereas for NSA (0.72, SE 0.03) this area was greatest in femoral neck fractures. These results confirm the association of BMD with proximal femur fracture and support the evidence that PFG plays a significant role only in neck fracture prediction, since NSA is the best predictive parameter among those tested. Received: 24 April 2001 / Accepted: 1 August 2001     

Case-Control Study of the Pathogenesis and Sequelae of Symptomatic Vertebral Fractures in Men

To investigate the pathogenesis and sequelae of symptomatic vertebral fractures (VF) in men, we have performed a case–control study, comparing 91 men with VF (median age 64 years, range 27–79 years) with 91 age-matched control subjects. Medical history, clinical examination and investigations were performed in all patients and control subjects, to identify potential causes of secondary osteoporosis, together with bone mineral density (BMD) measurements. BMD was lower at the lumbar spine and all sites in the hip in patients with VF than in control subjects (p<0.001). Potential underlying causes of secondary osteoporosis were found in 41% of men with VF, compared with 9% of control subjects (OR 7.1; 95% CI 3.1–16.4). Oral corticosteroid and anticonvulsant treatment were both associated with a significantly increased risk of VF (OR 6.1; 95% CI 1.3–28.4). Although hypogonadism was not associated with an increased risk of fracture, the level of sex hormone binding globulin was higher (p<0.001) and the free androgen index lower (p<0.001) in men with VF than control subjects. Other factors associated with a significantly increased risk of VF were family history of bone disease (OR 6.1; 95% CI 1.3–28.4), current smoking (OR 2.8; 95% CI 1.2–6.7) and alcohol consumption of more than 250 g/week (OR 3.8; 95% CI 1.7–8.7). Men with VF were more likely to complain of back pain (p<0.001) and greater loss of height (p<0.001) than control subjects, and had poorer (p<0.001) scores for the energy, pain, emotion, sleep and physical mobility domains of the Nottingham Health Profile. We conclude that symptomatic VF in men are associated with reduced BMD, underlying causes of secondary osteoporosis such as corticosteroid and anticonvulsant treatment, family history of bone disease, current smoking and high alcohol consumption, and that they impair the perceived health of the individual. Received: 23 February 1998 / Accepted: 13 May 1998     

Forearm Fractures as Predictors of Subsequent Osteoporotic Fractures

To assess the ability of distal forearm fractures to predict future fractures, we conducted a population-based retrospective cohort study among the 1288 residents (243 men, 1045 women) of Rochester, Minnesota age 35 years or older who experienced their first distal forearm fracture in 1975–94. During 9664 person-years of follow-up, 548 patients experienced 1109 subsequent fractures, excluding 195 that occurred on the same day as the index forearm fracture. The cumulative incidence of any subsequent fracture was 55% by 10 years and 80% by 20 years following the initial distal forearm fracture. Compared to expected fracture rates in the community, the risk of a hip fracture following the index forearm fracture was increased 1.4-fold in women (95% CI, 1.1–1.8) and 2.7-fold in men (95% CI, 0.98–5.8). In women, the risk of hip fracture differed by age, as we had found in a previous study. Women over age 70 had a 1.6-fold increase (95% CI, 1.2–2.0) in subsequent hip fracture risk whereas women who sustained their first forearm fracture before age 70 years did not have significantly increased risk. By contrast, vertebral fractures were significantly increased at all ages, with a 5.2-fold increase (95% CI, 4.5–5.9) in risk among women and a 10.7-fold increase (95% CI, 6.7–16.3) among men following a first distal forearm fracture. The increased risk in men suggests that a sentinel forearm fracture should not be ignored. Among the women, we also found a missed opportunity for intervention as hormone replacement therapy was underutilized. Received: 8 May 1998 / Accepted: 16 October 1998     

Quantitative Ultrasound and Symptomatic Vertebral Fracture Risk in Chinese Women

Quantitative ultrasound (QUS) is emerging as a simple, inexpensive and noninvasive method for assessing bone quality and assessing fracture risk. We assessed the usefulness of a contact calcaneal ultrasonometer by studying normal premenopausal women (group I, n= 53), normal postmenopausal women (group II, n= 198), and osteoporotic women without (group III, n= 141) and with vertebral fractures (group IV, n= 53). The osteoporotic subjects had a T-score of the spine or hip neck bone mineral density (BMD) <−2.5 based on the local Chinese peak young mean values. When compared with postmenopausal controls, mean broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) were 26%, 2.1% and 25% lower in women with vertebral fractures (p all <0.005). The correlation coefficients between QUS parameters and BMD of the spine and hip ranged between 0.4 and 0.5. The ability of the QUS to discriminate between patients groups was determined based on the mean value of normal premenopausal women in group I. The mean T-score for women with fractures was −2.87 ± 1.02 for BUA, −2.54 ± 0.79 for SOS, −3.17 ± 0.70 for QUI, −2.65 ± 0.86 for L2–4 BMD and −2.53 ± 0.66 for hip neck BMD. After adjustment for age and body mass index, the odds ratio of vertebral fracture was 1.71 (95% CI 1.2–2.6) for each 1 SD reduction in BUA, 2.72 (1.3–5.3) for SOS, 2.58 (1.4–4.6) for QUI, 2.33 (1.6–3.3) for L2–4 BMD, 2.09 (1.37–3.20) for femoral neck BMD and 1.88 (1.34–2.92) for total hip BMD. The association between the QUS parameters and vertebral fracture risk persisted even adjustment for BMD. The area under the receiver operating characteristic curve for BUA for vertebral fracture was 0.92, for SOS, QUI, L2–4 BMD and femoral neck BMD was 0.95, and for total hip was 0.91. Received: 7 January 1999 / Accepted: 18 May 1999     

Treatment of Glucocorticoid-Induced Osteoporosis with Alfacalcidol/Calcium Versus Vitamin D/Calcium

Vitamin D/calcium substitution is generally regarded as an effective first step treatment for glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to evaluate the efficacy of the active vitamin D metabolite alfacalcidol (1α) compared with the native vitamin D₃ in patients with established GIOP with or without vertebral fractures. Patients on long-term corticoid therapy were given either 1 μg alfacalcidol plus 500 mg calcium per day (group A, n = 43) or 1000 IU vitamin D₃ plus 500 mg calcium (group B, n = 42). The two groups were alike in age range, sex ratio, percentages of underlying diseases, average initial bone density values (lumbar spine: mean T-score −3.28 and −3.25, respectively), and rates of vertebral and nonvertebral fractures. During the 3-year study we found a small but significant increase of lumbar spine density in group 1α (+2.0%, P < 0.0001) and no significant changes at the femoral neck. In the D₃ group, there were no significant changes at both sites. At the end of the study, 12 new vertebral fractures had occurred in 10 patients of the group 1α and 21 in 17 patients of the D₃ group. In accordance with the observed fracture rates, the alfacalcidol group showed a significant decrease in back pain (P < 0.0001) whereas no change was seen in the vitamin D group. We conclude that with the doses used in this trial, alfacalcidol is superior to vitamin D in the treatment of established GIOP.     

Sex Difference in the Validity of Vertebral Deformities as an Index of Prevalent Vertebral Osteoporotic Fractures: A Population Survey of Older Men and Women

Morphometric methods have been developed for standardized assessment of vertebral deformities in clinical and epidemiologic studies of spinal osteoporosis. However, vertebral deformity may be caused by a variety of other conditions. To examine the validity of morphometrically assessed vertebral deformities as an index of osteoporotic vertebral fractures, we developed an algorithm for radiological differential classification (RDC) based on a combination of quantitative and qualitative assessment of lateral spinal radiographs. Radiographs were obtained in a population of 50- to 80-year-old German women (n= 283) and men (n = 297) surveyed in the context of the European Vertebral Osteoporosis Study (EVOS). Morphometric methods (Eastell 3 SD and 4 SD criteria, McCloskey) were validated against RDC and against bone mineral density (BMD) at the femur and the lumbar spine. According to RDC 36 persons (6.2%) had at least one osteoporotic vertebral fracture; among 516 (88.9%) nonosteoporotics 154 had severe spondylosis, 132 had other spinal disease and 219 had normal findings; 14 persons (2.4%) could not be unequivocally classified. The prevalence of morphometrically assessed vertebral deformities ranged from 7.3% to 19.2% in women and from 3.5% to 16.6% in men, depending on the stringency of the morphometric criteria. The agreement between RDC and morphometric methods was poor. In men, 62–86% of cases with vertebral deformities were classified as nonosteoporotic (severe spondylosis or other spinal disease) by RDC, compared with 31–68% in women. Among these, most had wedge deformities of the thoracic spine. On the other hand, up to 80% of osteoporotic vertebral fractures in men and up to 48% in women were missed by morphometry, in particular endplate fractures at the lumbar spine. In the group with osteoporotic vertebral fractures by RDC the proportion of persons with osteoporosis according to the WHO criteria (T-score <−2.5 SD) was 90.0% in women and 86.6% in men, compared with 67.9–85.0% in women and 20.8–50.0% in men with vertebral deformities by various methods. Although vertebral deformities by most definitions were significantly and inversely related to BMD as a continuous variable in both sexes [OR; 95% CI ranged between (1.70; 1.07–2.70) and (3.69; 1.33–10.25)], a much stronger association existed between BMD and osteoporotic fractures defined by RDC [OR; 95% CI between (4.85; 2.30–10.24) and (15.40; 4.65–51.02)]. In the nonosteoporotic group individuals with severe spondylosis had significantly higher BMD values at the femoral neck (p <0.01) and lumbar spine (p <0.0004) compared with the normal group. On the basis of internal (RDC) and external (BMD) validation, we conclude that assessment of vertebral osteoporotic fracture by quantitative methods alone will result in considerable misclassification, especially in men. Criteria for differential diagnosis as used within RDC can be helpful for a standardized subclassification of vertebral deformities in studies of spinal osteoporosis. Received: 5 February 1999 / Accepted: 24 June 1999     

Associations of Early Premenopausal Fractures with Subsequent Fractures Vary by Sites and Mechanisms of Fractures

In a retrospective population-based study we assessed whether and how self-reported former fractures sustained at the ages of 20–34 are associated with subsequent fractures sustained at the ages of 35–57. The 12,162 women who responded to fracture questions of the baseline postal enquiry (in 1989) of the Kuopio Osteoporosis Study, Finland formed the study population. They reported 589 former and 2092 subsequent fractures. The hazard ratio (HR), with 95% confidence interval (CI), of a subsequent fracture was 1.9 (1.6–2.3) in women with the history of a former fracture compared with women without such a history. A former low-energy wrist fracture was related to subsequent low-energy wrist [HR = 3.7 (2.0–6.8)] and high-energy nonwrist [HR = 2.4 (1.3–4.4)] fractures, whereas former high-energy nonwrist fractures were related only to subsequent high-energy nonwrist [HR = 2.8 (1.9–4.1)] but not to low-energy wrist [HR = 0.7 (0.3–1.8)] fractures. The analysis of bone mineral density (BMD) data of a subsample of premenopausal women who underwent dual x-ray absorptiometry (DXA) during 1989–91 revealed that those with a wrist fracture due to a fall on the same level at the age of 20–34 recorded 6.5% lower spinal (P= 0.140) and 10.5% lower femoral (P= 0.026) BMD than nonfractured women, whereas the corresponding differences for women with a former nonwrist fracture due to high-energy trauma were −1.8% (P= 0.721) and −2.4% (P= 0.616), respectively. Our results suggest that an early premenopausal, low-energy wrist fracture is an indicator of low peak BMD which predisposes to subsequent fractures in general, whereas early high-energy fractures are mainly indicators of other and more specific extraskeletal factors which mainly predispose to same types of subsequent fractures only. Received: 21 February 1996 / Accepted: 24 September 1996     

Physical Activity and Risk Factors for Hip Fractures in Thai Women

Hip fractures are among the most important causes of ill health and death among elderly people. Several potentially modifiable risk factors have been reported. Most claimed physical activity as a promising, inexpensive preventive measure for hip fracture. However, knowledge about risk factors for hip fracture in Asian populations is very limited. We therefore conducted a case–control study to assess the relationships between physical activity and risk of hip fractures in Thai women. From 14 hospitals in Thailand, 229 cases with a radiologically confirmed first hip fracture were enrolled. Two hundred and twenty-four controls were randomly recruited from the same neighborhood and were matched to the cases by age within a 5 year range. Information on physical activity as well as other potential confounders was obtained through personal interviews. Multivariate logistic regression revealed that past physical activity was protective in both very active and active women (OR = 0.67, 95% CI = 0.40–1.12 for moderately active women and OR = 0.20, 95% CI = 0.10–0.38 for very active women; p value for trend <0.01). Recent physical activity reduced the risk to about two-thirds (OR = 0.33, 95% CI = 0.19–0.60 and OR = 0.35, 95% CI = 0.18–0.69 for moderately and very active women respectively). In addition, breastfeeding was identified to be a protective factor (OR = 0.87, 95% CI = 0.80–0.94). In contrast, the following risk factors were identified: current use of antihistamine (OR = 13.96, 95% CI = 1.38–141.13) or traditional medicine (OR = 7.66, 95% CI = 2.71–21.63), underlying cerebrovascular diseases (OR = 6.53, 95% CI = 2.10–20.34), history of fracture (OR = 4.04, 95% CI = 1.26–12.99), parental Chinese racial background (OR = 2.52, 95% CI = 1.49–4.23), alcohol consumption (OR = 2.30, 95% CI = 1.04–5.09). Received: 14 April 2000 / Accepted: 17 October 2000     

A Population-Based Study of Fracture Incidence in Southern Tasmania: Lifetime Fracture Risk and Evidence for Geographic Variations within the Same Country

Symptomatic fractures are a significant problem in terms of both morbidity and financial cost. Marked variation in both total and site-specific fracture incidence has been documented internationally but there is limited within-country data. This prospective population-based study documented the incidence of all symptomatic fractures occurring from July 1, 1997 to June 30, 1999 in adults ≥50 years of age resident in Southern Tasmania (total population ≥50 years: 64 688). Fractures were ascertained by reviewing reports from all the radiology providers within the area. There were 701 fractures in men and 1309 fractures in women. The corresponding fracture incidence in men and women was 1248 and 1916 per 100 000 person-years, respectively. Residual lifetime fracture risk in a person aged 50 years was 27% for men and 44% for women with fractures other than hip fractures constituting the majority of symptomatic fracture events. These fracture risk estimates remained remarkably constant with increasing age. In comparison to Geelong, there were significantly lower hip fracture rates (males: RR 0.59, 95% CI 0.45–0.76; females: RR 0.61, 95% CI 0.53–0.71) but significantly higher distal forearm fractures (males: RR 1.87, 95% CI 1.10–3.78; females: RR 1.31, 95% CI 1.11–1.55) and total fractures in men (RR 1.31, 95% CI 1.17–1.46) but not women (RR 1.05, 95% CI 0.98–1.13). In contrast, Southern Tasmania had lower age-standardized rates of all fractures compared with Dubbo (RR 0.28–0.79). In conclusion, this study provides compelling evidence that fracture incidence varies between different geographic sites within the same country, which has important implications for health planning. In addition, the combination of high residual fracture risk and short life expectancy in elderly subjects suggests fracture prevention will be most cost-effective in later life. Received: 27 April 2000 / Accepted: 16 August 2000     

Systematic review of the benefits and harms of calcitriol and alfacalcidol for fractures and falls

Our objective was to conduct a systematic review on the benefits and harms of calcitriol and alfacalcidol in the reduction of fracture and fall risk. Randomized controlled trials (RCTs) comparing these agents to placebo or calcium and reporting fracture and fall incidence were retrieved from MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Two reviewers independently determined study eligibility, assessed trial quality, and extracted data. Twenty-three RCTs were included (2139 participants), and 16 trials had sufficient data for meta-analysis. Vertebral fractures were not significantly reduced based on the combined results of 13 trials; however, subgroup analyses demonstrated a significant reduction with alfacalcidol [odds ratio (OR) = 0.50, 95% confidence interval (CI), 0.25–0.98], but not with calcitriol. There was a significant reduction in nonvertebral fractures (six trials, OR = 0.51, 95% CI, 0.30–0.88), and falls (two trials, OR = 0.66, 95% CI, 0.44–0.98). There was an increased risk of hypercalcemia (OR = 3.63, 95% CI, 1.51–8.73) and a trend toward an increased risk of hypercalciuria. There is evidence to suggest that these agents may reduce the incidence of nonvertebral fractures and falls; however, their benefit on vertebral fracture reduction may depend on the type of active vitamin D. Hypercalcemia and hypercalciuria are potential side effects.