Bone Mineral Densitometry Substantially Influences Health-Related Behaviors of Postmenopausal Women

Although bone mineral density measurements are helpful in predicting future risk for osteoporotic fractures, there is limited information available on how the results of bone densitometry influence a woman's use of therapeutic alternatives. To assess the role of bone mineral densitometry in influencing postmenopausal women to change health behaviors associated with osteoporosis, we prospectively followed, for an average of 2.9 years, 701 postmenopausal women over 50 years of age referred to an osteoporosis prevention program in a large metropolitan area. Assessments included bone mineral densitometry by dual-energy X-ray absorptiometry (with classification of skeletal health), medical history, use of hormone replacement therapy, calcium intake, caffeine intake, exercise, smoking habits, and fall precaution measures. Women classified at baseline with moderate low bone mass were twice as likely (33%), and women with severe low bone mass more than three times as likely (47%) to start hormone replacement therapy compared with women with a normal result (13%, P < 0.001). This was true regardless of whether they had taken hormone replacement therapy in the past. Below-normal BMD was a strong predictor of a woman's initiation of hormone replacement therapy (OR 4.2; 95% CI 2.7–6.4; P < 0.05) even after adjustment for age, education, history of osteoporosis or fracture, and medical condition related to osteoporosis. Women with moderate or severe low bone mass were also much more likely to start calcium supplements (81–90% versus 67%), increase dietary calcium (71–82% versus 60%), decrease use of caffeine (44–60% versus 34%), start exercising (61–76% versus 52%), and quit smoking (22–24% versus 11%) relative to their behaviors prior to testing (P < 0.01). In conclusion, postmenopausal women report that the results of bone densitometry substantially influence the decision to begin hormone replacement therapy and calcium supplements, increase dietary calcium, decrease caffeine, increase exercise, decrease smoking, and take precautions to prevent falls. More studies are needed to measure the long-term effects of this influence. Received: 19 March 1999 / Accepted: 13 August 1999     

Prolonged Progressive Calcaneal Bone Loss Despite Early Weightbearing Rehabilitation in Patients Surgically Treated for Achilles Tendinosis

We prospectively evaluated areal bone mineral density (BMD) of the calcaneus and calf-muscle strength (concentric and eccentric plantar flexion peak torque in Nm) in 10 recreational athletes (5 males and 5 females), mean age 40.9 years (range 26–55), who were selected to undergo surgical treatment for chronic Achilles tendinosis localized at the 2–6 cm level. Surgery was followed by immobilization in a plaster cast for 2 weeks, followed by flexibility training and slowly progressing strength training and weight-bearing activity. One patient was excluded after week 0 because of a new injury. Seven patients were back to their preinjury activity at the 26-week control, and eight patients at the 52-week control postoperatively. BMD in the calcaneus and calf-muscle strength on the injured and noninjured side was measured preoperatively (week 0) and postoperatively (weeks 2, 6, 16, 26, and 52). There were no significant differences in BMD between the injured and noninjured side at weeks 0, 2, and 6, but at weeks 16, 26, and 52, BMD was significantly (P < 0.05) lower (11.5%, 18.4%, and 16.4%, respectively) in the calcaneus of the injured side. Concentric and eccentric plantar flexion strength were significantly lower on the injured side preoperatively. Eccentric, but not concentric plantar flexion strength had recovered compared with the noninjured side 1 year postoperatively. Calf-muscle strength was not related to bone mass in the calcaneus. As a comparison, we used a group of 11 recreational athletes (10 males and 1 female), with a mean age of 46.1 years (range 28.9–58.5) who had been surgically treated for chronic Achilles tendinosis at the 2–6 cm level 39.5 ± 11.8 months ago. In this group, there was no significant difference in BMD of the calcaneus between the injured and noninjured side. It seems that there was a delayed and prolonged calcaneal bone loss despite early weightbearing loading in patients surgically treated for chronic Achilles tendinosis at the 2–6 cm level. Around that time, when the Achilles tendon had healed (4–6 months) and the athletes returned to their sports, the calcaneal bone had a relatively low BMD and might possibly be vulnerable to heavy loadings. There were no signs of recovery 1 year postoperatively, but in a comparison group there were no significant side-to-side differences 39.5 months postoperatively. Received: 31 December 1996 / Accepted: 21 May 1997     

Stiffness in Discrimination of Patients with Vertebral Fractures

We measured the ultrasound parameters of the heels of 49 women with vertebral fractures and 87 age-matched controls using an Achilles ultrasound device. Average broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness were significantly lower in fracture patients (p<0.0001). We also estimated the ultrasound parameters of patients compared with age-matched non-fracture controls and found the mean BUA to be −1.02 SD below control values. The mean SOS was −0.97 SD and the mean Stiffness was −1.12 SD below control values.  Femoral bone mineral density (BMD) at the neck, Ward’s triangle and the trochanter, the total-body BMD and L2–4 BMD were measured with dual-energy X-ray absorptiometry (DXA) and found to be significantly lower in fracture patients (p<0.0001). All correlation coefficients between ultrasound parameters and DXA measurements were >0.5 and statistically significant (p<0.0001). A stepwise logistic regression with presence or absence of vertebral fracture as the response variable and all ultrasound – DXA parameters as the explanatory variables indicated that the best predictor of fracture was Stiffness, with additional predictive ability provided by spine BMD. Sensitivity and specificity of all measures were determined by the areas under the receiver operating characteristic (ROC) curve, which were 0.76 ± 0.04 for BUA, 0.77 ± 0.04 for SOS, 0.78 ± 0.04 for Stiffness and 0.78 ± 0.03 for spine BMD. The areas under the ROC curves of BUA, SOS, Stiffness and spine BMD were compared and it was found that Stiffness and spine BMD were significantly better predictors of fracture than BUA and SOS. These results support many recent studies showing that ultrasound measurements of the os-calcis have diagnostic sensitivity comparable to DXA, and also demonstrated that Stiffness was a better predictor of fracture than spine BMD. Received: 23 September 1997 / Accepted: 10 April 1998     

The Urinary Excretion of Deoxypyridinium Cross-Links is Higher in Diabetic Than in Nondiabetic Adolescents

We have measured the urinary excretion of deoxypyridinium (D-Pyr) crosslinks, a sensitive and specific marker of bone resorption, in morning urine in 102 healthy, nonhospitalized, Caucasian subjects (8–18 years) and in 18 diabetic subjects (12–17 years). The free D-Pyr crosslinks were measured using the Pyrilinks D-Assay. In the diabetic subjects, plasma glucose was regulated throughout the night by a constant infusion of insulin and a variable infusion of 24% glucose. In the nondiabetic subjects, the excretion of D-Pyr increased until 12–14 years of age, and thereafter decreased, and the excretion of D-Pyr/hour was correlated with the height Z-score. The excretion of D-Pyr/hour and the D-Pyr/creatinine ratio was higher in the diabetic adolescents than in the nondiabetic adolescents. In subjects over the age of 12, the D-pyr/creatinine ratio was higher in males than in females. In conclusion, in healthy children and adolescents, the excretion of D-Pyr peaks at 12–14 years of age. The D-Pyr excretion is higher in diabetic than in nondiabetic adolescents, suggesting increased bone resorption in diabetic adolescents. Received: 8 May 1997 / Accepted: 10 January 1999     

Urinary Excretion of Type I Collagen Degradation Products in Healthy Women and Osteoporotic Patients with Vertebral and Hip Fractures

We have evaluated both the effect of normal aging and menopause on urinary CrossLaps™ (u-CTx) excretion and the bone resorption status by u-CTx in patients with vertebral fracture and hip fracture. In 246 healthy women, 76 patients with vertebral fracture, and 63 patients with hip fracture, u-CTx excretion was measured by ELISA. The age-related changes of u-CTx in healthy females reflected the marked increase of bone resorption associated with modeling at childhood. The values in the subgroups of postmenopausal women 1–3 years since menopause and ≤10 years since menopause were significantly higher than those in the subgroups of premenopausal adult women. The values in the vertebral fracture group were significantly higher than those in the premenopause group, but not those in the postmenopause groups. The values in the hip fracture group were significantly higher than those in the other groups. Of the 70 postmenopausal subjects aged 45–64 years, 43% had u-CTx values more than 2 SD above premenopausal mean. The corresponding values in the patients with vertebral fracture and those with hip fracture were 58% and 64%, respectively. This marker reflects well the increase of bone resorption associated with bone modeling at childhood and with high bone turnover after menopause. The excretions in the patients with hip fracture were much higher than those in the age-matched subjects and also higher than those in the patients with vertebral fracture. These findings indicate that the abnormality of bone resorption in the patients with hip fracture is more severe than in the patients with vertebral fracture. Received: 30 January 1997 / Accepted: 7 August 1997     

Bone Mineral Density and Biochemical Markers of Bone Turnover in Peri- and Postmenopausal Women

Bone mineral density (BMD) measured by densitometry is the elective parameter for the diagnosis of osteopenia and osteoporosis. Biochemical markers have been proposed as sensitive indicators of high bone turnover and for monitoring response to antiresorptive treatment. We conducted a retrospective study to investigate the values of biochemical markers of bone metabolism with a view to early diagnosis of osteoporosis and monitoring of hormone replacement and calcitonin therapy. The subjects were 415 women, mean age 51 ± 8 years (43–62 years) in peri- and postmenopause, recruited at the Menopause Center of Obstetrics and Gynecology Department of Siena University and divided in five groups. Bone densitometry was performed in all subjects and blood samples were taken for assayed biochemical markers, that is, [osteocalcin (OC), parathyroid hormone (PTH), type 1 procollagen (PICP), and calcitonin (CT)]. Three groups of women were divided into two subgroups: those with normal and those with low BMD (<1 SD). Basal concentrations of PCP1, OC, PTH, and CT were compared in the various groups. Two groups of postmenopausal women with BMD below the normal were treated with estrogen replacement therapy and unmodified eel calcitonin. We evaluated whether some of these biochemical markers of bone turnover could help identify women with low BMD and whether they could be useful for monitoring the results of antiresorptive therapies. Markers of bone formation (PICP and OC) make it possible to distinguish women with high turnover who are at risk for osteoporosis from women with low turnover in menopause. A good correlation was also found between changes in levels of these markers and changes in BMD during treatments, which suggests that the PICP and OC would be useful for monitoring response to antiresorptive therapy. Received: 29 March 1998 / Accepted: 2 November 1999     

Osteoporosis in Male and Female Leprosy Patients

We measured the bone mineral density (BMD) of 353 leprosy patients (197 males 50–89 years old, average age 70.2; and 156 females 53–90 years old, average age 72.9) and serum levels of free testosterone (FT) in 81 males. The BMD of the lumbar vertebrae (L2–L4), diaphysis of the radius (1/3 radius), and the neck of the femur (neck) was measured using DXA (QDR 4500). The BMD of −2.5 SD YAM (young adult mean) in Japanese men and women was used as the cutoff value for osteoporosis in the respective genders: BMD of L2–L4, 0.751 g/cm² (male), 0.747 g/cm² (female); 1/3 radius, 0.655 g/cm² (male), 0.550 g/cm² (female); neck, 0.581 g/cm² (female). The percentages of males with osteoporosis were 31.3% in the 50th, 32.9% in the 60th, 44.9% in the 70th, and 40.7% in the 80th decade at L2–L4. Similarly, the percentages were 33.3%, 58.3%, 74.3%, and 75.0%, respectively, at 1/3 radius. Among females, the percentages were 22.2%, 41.3%, 44.9%, and 68.8%, respectively, at L2–L4; 0%, 42.9%, 89.5%, and 78.6%, respectively, at 1/3 radius; and 11.1%, 38.6%, 67.7%, and 84.6% respectively, at neck. FT in men ranged from almost 0 to normal at each decade and BMD levels were significantly correlated with FT in all three regions of the skeleton (P < 0.0001). More than 30% of osteoporosis was found at each decade and FT may be one of the main factors affecting BMD in male leprosy patients. Received: 6 February 1998 / Accepted: 9 July 1998     

Ultrasound Bone Densitometry of the Os Calcis in Children and Adolescents

The aim of the present investigation was to evaluate reference data and to examine whether there were weight-, height-, age-, and sex-related differences of the quantitative ultrasound bone parameters for healthy children and adolescents. A total of 3299 healthy Caucasian children and teenagers (1623 girls and 1676 boys), age range from 6–18 years (mean age 11.4 ± 3.4 years for boys and mean age 11.5 ± 3.3 years for girls) were examined by quantitative ultrasound densitometry (QUS) using the bone sonometer SAHARA (Hologic Inc., Waltham, MA, USA), a waterless, dry system. The parameters broadband ultrasound attenuation (BUA) [dB/MHz] and speed of sound (SOS) [m/second] were evaluated on the right heel in relation to age, sex, weight, and height. There is no correlation between the ultrasound bone parameter SOS and age, height, and weight. BUA increases with age, height, and weight. Significant differences in SOS and BUA between girls and boys were found to probably be caused by the different onset of growth phases and the onset of puberty. SOS and BUA are influenced by changes of bone mineral density. But BUA is dependent on bone size, too. In conclusion, ultrasound bone densitometry is a useful measuring method showing the physiological bone development in childhood and adolescence. The presented results can be used as reference data. Further studies in children with disorders influencing bone metabolism will show in what way various patterns of osteopenia in childhood can be detected. Received: 20 August 1999 / Accepted: 20 April 2000 / Online publication: 22 September 2000     

The Effects of 10 Weeks Military Training on Heel Ultrasound and Bone Turnover

To measure the physiological changes in bone in response to strenuous exercise we performed a prospective study of male army recruits over 10 weeks of basic training. Measurements performed at the start and completion of training consisted of ultrasound (US) measurements of the heel: velocity of sound (VOS in m/seconds) and broadband ultrasound attenuation (BUA in dB/MHz) and bone turnover markers; osteocalcin (OC), bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase (TRAP). Forty subjects were recruited for the study and 26 completed training. Over the 10-week study period there was a significant 1.7% fall in mean VOS [mean paired difference (mpd) 27.2 m/second, SEM 9.5 (95% CI 7.5–46.8) P= 0.009] and a nonsignificant 3.4% increase in BUA (P= 0.159). There were significant falls in markers of bone formation OC [11.6%, mpd 0.11 μg/liter (95% CI 0.07–0.14) P < 0.001] and BALP [13.3%, mpd 3.49 U/liter (CI 0.80–6.18) P= 0.013] and a nonsignificant 9.5% fall in TRAP a marker of bone resorption. The 10 recruits subsequently injured had a significantly lower VOS on entry [mean difference 24.2 m/seconds (95% CI 4.6–43.7) P= 0.017] and nonsignificantly raised BUA and baseline levels of all bone markers. The ultrasound changes may be accounted for by increase in trabecular separation and a fall in trabecular connectivity due to microfracture. The decrease in bone markers implies a fall in bone turnover. Received: 26 June 1997 / Accepted: 26 August 1998     

Quantitative Ultrasound and Bone Mineral Density in Patients with Primary Hyperparathyroidism Before and after Surgical Treatment

The aim of this study was to assess the pattern of ultrasound (QUS) parameters and bone mineral density at different skeletal sites in patients with primary hyperparathyroidism (PHPT) before and after surgical treatment. In 22 patients (age range 28–74 years) with PHPT we measured speed of sound (SOS), attenuation (BUA) and Stiffness at the calcaneus, amplitude-dependent speed of sound (AD-SoS) at proximal phalanges, and bone mineral density at lumbar spine (BMD-LS) and at the mid-radius (BMD-MR) and ultradistal radius (BMD-UDR) before, 1 and 2 years after surgical operation. Twenty-two age- and sex-matched healthy subjects provided control data. Before surgery, all parameters apart from SOS were significantly lower in PHPT patients than in controls. At the end of the study period, BMD-LS increased by 7.0%, BMD-UDR by 7.4% and BMD-MR by 11.0%. The changes in ultrasound parameters after surgery were lower (0.44% for SOS, 2.2% for BUA, 3.3% for Stiffness and 2.6% for AD-SoS); however, the increase was statistically significant (p<0.05 and p<0.01, respectively) only for Stiffness and AD-SoS. Our results indicate that parathyroidectomy increases both axial and appendicular BMD and influences QUS parameters differently at the calcaneus and at the phalanges. The combined use of BMD and QUS could improve the assessment of skeletal status in patients with PHPT before and after surgery. Received: 22 January 1999 / Accepted: 25 August 1999     

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     

Vitamin D Binding Protein Gene in Male Osteoporosis: Association of Plasma DBP and Bone Mineral Density with (TAAA)n-Alu Polymorphism in DBP

Vitamin D binding protein (DBP) is a major carrier protein for the vitamin D metabolites, but may also play an important role in osteoclast differentiation. Polymorphisms of the DBP gene have been reported, including (TAAA)_n-Alu repeat polymorphisms downstream of intron 8. We have examined the relationship between polymorphisms of the DBP gene and bone mineral density (BMD) and vertebral fractures in a group of 26 men with vertebral fractures but no underlying secondary cause of osteoporosis (median age 64, ages 27–72 years) and 21 male control subjects (median age 65, ages 40–77 years). There was no apparent effect of DBP phenotype on BMD, but there was a relationship between certain genotypes of (TAAA)_n-Alu repeats and reduced BMD and vertebral fracture. Lumbar spine and femoral neck BMD were significantly lower in men with 10/8 genotype than 10/10 genotype (P < 0.05). Furthermore, the predominant genotype in men with vertebral fractures was 10/8, whereas the most common genotype in control subjects was 10/10 (odds ratio 56; 95% confidence interval 7–445). Plasma DBP was higher in men with 10/8 genotype than those with 10/10 genotype (P < 0.05), and patients with vertebral fractures were found to have higher levels than control subjects (P < 0.0005). Although our study is small because of the relative rarity of idiopathic osteoporosis in men, the results suggest that (TAAA)_n-Alu polymorphism may have an important effect on plasma levels of DBP, bone density and fracture risk in men. Received: 5 May 1998 / Accepted: 10 April 1999     

Bone ultrasonometry and turnover markers in primary hyperparathyroidism

Quantitative ultrasound (QUS) of bone and new markers of bone remodeling have been poorly investigated in mild primary hyperparathyroidism (PHPT). In this study 26 patients (20 females and 6 males) were evaluated. BUA and SOS were measured by QUS at the heel. Markers of bone remodeling assessed were bone alkaline phosphatase (BAP), osteocalcin (OC), procollagen type I N- and C-terminal propeptides (PINP et PICP), and procollagen type I C-terminal telopeptide in blood and urine (ICTP and CTX). Bone mineral density (BMD) was measured at the lumbar spine (LS), femoral neck (FN), and Ward's triangle (WT). The control group comprised 35 sex- and age-matched subjects. The statistically significant variables between the two groups were (P < 0.05) BUA, BMD_LS, BMD_FN, BMD_WT, BAP, and OC. Corresponding z-scores were −0.55 ± 0.75, −0.66 ± 0.77, −0.66 ± 0.71, −0.67 ± 0.52, 1.87 ± 3.87, and 1.93 ± 3.53, respectively. Although PICP and PINP levels were higher in PHPT patients as compared with controls, the difference was not significant. Several markers of bone turnover were moderately correlated with both QUS (r =−0.39 to −0.55) and BMD (r =−0.48 to 0.63). In conclusion QUS seems to be a relevant tool in the assessment of bone status for patients with mild PHPT. Received: 1 October 1998 / Accepted: 1 July 1999     

Clinical Observations with a New Specific Assay for Bone Alkaline Phosphatase: A Cross-Sectional Study in Osteoporotic and Pagetic Subjects and a Longitudinal Evaluation of the Response to Ovariectomy,Estrogens, and Bisphosphonates

The purpose of this study was to examine the serum levels of bone alkaline phosphatase (BALP) measured with a new assay in normal and in osteoporotic women, and to evaluate prospectively its responsiveness to changes of bone metabolism. The following groups of subjects were studied: (1) 95 healthy women (44–75 years) (22 pre- and 73 postmenopausal) and 35 osteoporotic women [vertebral bone mineral density (BMD) more than 2.5 SD below the normal adult mean]; (2) 10 women (44–50 years) ovariectomized (OVX) for benign uterine diseases, examined before and 12 months after surgery; (3) 16 OVX women (36–54 years), examined before and after 12 months of transdermal estrogen replacement therapy (50 μg/day); (4) 12 previously untreated pagetic patients (4 women and 8 men, 50–80 years), examined before and 3 months after the I.V. administration of clodronate (600 mg) or alendronate (5 mg) for 2 consecutive days. The median BALP value was 11.6 U/liter (25–75th percentiles: 10.5–12.7; range 7.7–19.3) in healthy premenopausal (PreMP) women and significantly higher (median: 16.8 U/liter; 25–75th percentile: 13.8–21.8; P < 0.01) in postmenopausal (PostMP) women. There was a clear age-related increase in normal subjects (r = 0.43; P < 0.001). In the osteoporotic group, BALP levels, as well as other biochemical parameters of bone turnover, were not significantly different from those of normal women when adjusted for age. In OVX women, BALP levels showed a marked increase 12 months after surgery (median: 113%; 25–75th percentile: 87–139%), significantly higher than the increase of total ALP (median: 43%; 25–75th percentile: 25–66%; P < 0.001), and similar to the increases of serum osteocalcin and urinary hydroxyproline. Transdermal estrogen treatment prevented the BALP increase, even if no reduction was observed; total ALP showed a similar behavior. The basal levels of BALP were significantly elevated in pagetic patients (median: 91 U/liter; range 18–610 U/liter) and correlated to the scintigraphic extent of the disease (r = 0.76; P < 0.01). Three months after the I.V. administration of bisphosphonates, the decrease of BALP was more marked than that of total ALP (median: −54% versus −41%; P < 0.05). In conclusion, these results suggest that BALP measurement with this immunoassay may be clinically useful, and more sensitive than total ALP, in the assessment of bone turnover during changes of the estrogen status as well as in monitoring the effects of treatments that modify the metabolic activity of the skeleton. Received: 25 January 1996 / Accepted: 3 May 1996     

The Tromsø Study: Artifacts in Forearm Bone Densitometry – Prevalence and Effects

Suboptimal performance of bone densitometer, operator and/or subject may cause artifacts of consequence both for individual patient management and research. The prevalence and effects of such artifacts are largely unknown in densitometry. A cross-sectional population-based study was carried out of artifacts in forearm bone densitometry with single X-ray Absorptiometry (SXA) of the nondominant hand (distal and ultradistal site). After the screening, all scans were reviewed for artifact detection and reanalysis. The effect on the bone mineral density (BMD) result was found by comparing artifactual scans with a reanalyzed version or with normal repeat scans. All women aged 50–74 years, all men aged 55–74 years and 5–10% samples of other age groups aged ≥25 years attending the fourth Troms? health study were invited to have bone densitometry. The response rate from the background population was 80% (n= 7948). Fourteen percent of subjects had a movement artifact at either the distal or ultradistal site. The individual BMD variation was twice as large in scans with a movement artifact (0.94%) compared with normal scans (0.58%) (p= 0.0027). The radial endplate was inaccurately detected in 74% of the scans. Reanalysis of these scans led to a mean 3.8% decrease in the BMD value and an increase in the prevalence of osteoporosis of 10%. Artifacts were thus common, and their effects were clinically relevant in forearm bone densitometry. Artifacts and their effects need to be characterized in other bone densitometry settings also. Received: 25 February 1999 / Accepted: 3 May 1999     

Differential Effects of Primary Hyperparathyroidism on Ultrasound Properties of Bone

Primary hyperparathyroidism (PHPT) may result in greater cortical than trabecular bone loss. Ultrasound is able to predict osteoporotic fracture risk independent of densitometric measurements, but little is known about the changes in ultrasound variables with PHPT. The aim of our study was to examine the effect of PHPT on ultrasound variables and bone density measurements at cortical (hand) and trabecular (lumbar spine and heel) sites, and to evaluate their reversibility following surgical treatment. We recruited 25 postmenopausal women diagnosed with PHPT ages 51–76 years (mean 62 years) and 95 postmenopausal controls ages 57–80 years (mean 67 years). Measurements were made at baseline and 1 year. Speed of sound (SOS) and broadband ultrasound attenuation (BUA) of the heel were measured using the Lunar Achilles (LA+) and McCue CUBA Clinical (CC). Amplitude-dependent speed of sound (AD-SoS) and ultrasound bone profile index (UBPI) of the fingers were measured using the IGEA DBM Sonic. Bone mineral density (BMD) of the hand and lumbar spine (LS) were measured by dual-energy X-ray absorptiometry (DXA). At baseline, hand BMD, LS BMD and heel BUA were significantly lower and finger UBPI significantly higher in the PHPT patients compared with controls (p<0.001). There were no differences in Stiffness Index, heel SOS or finger AD-SoS between control and PHPT subjects. At 1 year postoperatively, there was a mean (±SD) increase in LS and hand BMD of 3 ± 1% (p<0.01). BUA at the heel increased (11 ± 5%, p<0.001), and UBPI of the fingers decreased (17 ± 7%, p<0.001) probably reflecting different modes of attenuation in trabecular (scattering) and cortical (absorption) bone. Stiffness Index, SOS of the heel and AD-SoS of the fingers did not change. BUA, UBPI and BMD returned towards normal postmenopausal values following surgery. There were no changes in BMD or QUS variables at 1 year in the control group. Quantitative ultrasound (QUS) measurements provide different information about bone structure than densitometric measurements and cannot be regarded as simply reflecting bone density. With further research the combined use of BMD and QUS could improve the assessment of skeletal status in patients with PHPT before and after surgery. Received: 10 September 2001 / Accepted: 31 January 2002     

Quantitative ultrasound imaging of the calcaneus: precision and variations during a 120-Day bed rest

This study reports on the precision and variation of quantitative ultrasound (US) parameters [broadband ultrasonic attenuation (BUA) or slope of the frequency-dependent attenuation in dB/MHz and speed of sound (SOS m/second)] after 120 days of continuous bed rest in six normal male volunteers. Quantitative US was measured at the calcaneus using a new US bone imaging scanner. The measurements were carried out on both heels at approximately 2-week intervals. The short-term precision was 0.31% for SOS and 2.8% for BUA. The long-term precision was 0.58% for SOS, 4.7% for BUA. A significant decrease of SOS values of −26 m/second (P < 0.0001) for the right heel and −17 m/second (P < 0.05) for the left heel was found at the group level. In terms of percentage change this represents −1.7% for the right heel and −1.1% for the left heel. These percentage decrements were 3.5–5.5 times that of the short-term precision and 2–3 times that of the long-term precision of the technique. At the individual level, the decrease of SOS was statistically significant (P < 0.05) or marginally significant (P < 0.1) for four out of 6 subjects. For 2 other subjects, similar trends were observed, but without reaching statistical significance. BUA did not change significantly during follow-up. These results are consistent with previous findings on changes of ultrasonic properties from the calcaneus during aging, pregnancy, or therapy, showing that calcaneus SOS is a valuable index of bone loss. These preliminary data suggest that prolonged exposure to simulated weightlessness may lead to a lower SOS, which then could be used for the follow-up of bone demineralization occurring during long-term space flights. Received: 5 January 1999 / Accepted: 1 July 1999     

Prediction of Osteoporotic Fractures by Bone Densitometry and COLIA1 Genotyping: A Prospective, Population-Based Study in Men and Women

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mineral density and increased fracture risk. Although the genetic basis of osteoporosis is incompletely understood, previous studies have identified a polymorphism affecting an Sp1 binding site in the COLIA1 gene that predicts bone mineral density and osteoporotic fractures in several populations. Here we investigated the role of COLIA1 genotyping and bone densitometry in the prediction of osteoporotic fractures in a prospective, population-based study of men (n= 156) and women (n= 185) who were followed up for a mean (± SEM) of 4.88 ± 0.03 years. There was no significant difference in bone density, rate of bone loss, body weight, height, or years since menopause between the genotype groups but women with the “ss” genotype were significantly older than the other genotype groups (p= 0.03). Thirty-nine individuals sustained 54 fractures during follow-up and these predominantly occurred in women (45 fractures in 30 individuals). Fractures were significantly more common in females who carried the COLIA1“s” allele (p= 0.001), although there was no significant association between COLIA1 genotype and the occurrence of fractures in men. Logistic regression analysis showed that carriage of the COLIA1“s” allele was an independent predictor of fracture in women with an odds ratio (OR) [95% CI] of 2.59 [1.23–5.45], along with spine bone mineral density (OR = 1.57 [1.04–2.37] per Z-score unit) and body weight (OR = 1.05 [1.01–1.10] per kilogram). Moreover, bone densitometry and COLIA1 genotyping interacted significantly to enhance fracture prediction in women (p= 0.01), such that the incidence of fractures was 45 times higher in those with low BMD who carried the “s” allele (24.3 fractures/100 patient-years) compared with those with high BMD who were “SS” homozygotes (0.54 fracture/100 patient-years). We conclude that in our population, COLIA1 genotyping predicts fractures independently of bone mass and interacts with bone densitometry to help identify women who are at high and low risk of sustaining osteoporotic fractures. Received: 16 November 2000 / Accepted: 9 June 2000     

Walking after Stroke: Does It Matter? Changes in Bone Mineral Density Within the First 12 Months after Stroke. A Longitudinal Study

Stroke patients have increased risk of hip fractures. Nearly all fractures occur on the hemiplegic side, and reduced bone mineral density (BMD) may be an important predisposing factor. The aim of this study was to investigate the degree of demineralization within the first year after stroke, and to elucidate a possible difference in patients with high versus low ambulatory levels. Forty acute stroke patients were followed (17 initially wheelchair-bound and 23 initially ambulatory). BMD was measured in the proximal femur bilaterally at a mean 6 days, 7 months and 1 year after stroke onset using dual-energy X-ray absorptiometry. Ambulatory status was independently associated with changes in BMD (p≤0.005) 1 year after stroke. The 17 initially wheelchair-bound patients had a significant 10% reduction in BMD at the paretic side and 5% reduction at the non-paretic side (p<0.001), while the 23 patients initially able to walk had a significant loss (3%) only at the paretic side (p = 0.01). The analysis also indicated that the major reduction in BMD took place within the first 7 months. Two months after stroke 12 of the wheelchair-bound patients had relearned to walk. At the paretic side the 1 year changes in BMD in the patients who stayed wheelchair-bound, the patients who relearned to walk within the first 2 months and the patients who were able to walk throughout the study were 13%, 8% and 3%, respectively, and a statistically significant trend with ambulatory level was found (p = 0.007). This study provides clear evidence that lack of mobility and weight-bearing early after stroke is an important factor for the greater bone loss in the paretic leg, but that relearning to walk within the first 2 months after stroke, even with the support of another person, may reduce the bone loss after immobilization. Received: 24 August 1999 / Accepted: 25 October 1999     

Quantitative Ultrasound of the Heel and Some Parameters of Bone Turnover in Patients with Acromegaly

Acromegaly caused by growth hormone (GH) hypersecretion is characterized by enhanced skeletal growth and soft tissue enlargement. Insulin-like growth factor-1 (IGF-1) is the main peripheral mediator of GH action and it has a crucial role in the maintenance of a normal bone mass. However, in some patients with acromegaly, secondary osteoporosis is observed, despite the strong anabolic effect of GH and IGF-1 in bones. It is thought to be due to hypogonadism. The bone changes are accompanied by increased turnover. The aim of this study was to assess bone properties by ultrasound and turnover in patients with acromegaly. The study was carried out in 26 patients (13 men, 13 women): 14 with active acromegaly and 12 cured by surgery who had non-active disease. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and their combination Stiffness Index (SI) by quantitative ultrasound (QUS) of the heel, hormonal status, serum osteocalcin (OC) concentration and the urinary excretion of pyridinoline collagen crosslinks (PYR) were all studied. Controls were 20 age- and sex-matched healthy persons. We observed statistically significantly lower QUS values in patients with active disease than in those whose disease was cured. The differences were more pronounced in men. QUS values were lower in the entire group of patients compared with the controls; however, the differences were not statistically significant. Serum OC concentrations and urinary PYR excretion were higher in active disease. Statistically significant inverse correlations between serum GH levels and SOS (r=–0.58, p = 0.002); BUA (r=–0.66; p= 0.0001); T-score (r = −0,65, p= 0.0001) and Z-score (r=–0.66, p = 0.0001) were found only in male patients. No correlations between IGF-1, duration of the disease, OC, PYR and other data studied were observed. In conclusion, we have shown decreased QUS parameters suggesting impaired bone properties and quality in terms of density and elasticity in men, but not in women, with active acromegaly. This finding suggests osteoporosis with increased bone turnover. The above-mentioned changes might be caused by the action of GH on trabecular bone and its metabolism, since no hypogonadism in male patients was shown. Moreover, the influence of acromegaly on heel geometry and soft tissue swelling should also be considered. Received: 20 February 2001 / Accepted: 23 October 2001