Paul Gerdhem

Biochemical Markers of Bone Metabolism and Prediction of Fracture in Elderly Women

We studied the ability of various markers of bone turnover to predict fracture in 1040 randomly recruited 75‐year‐old women. A total of 178 of the women sustained at least one fracture during follow‐up (mean, 4.6 years). In elderly women, TRACP5b and urinary fragments of osteocalcin are promising new markers for prediction of fracture, in particular, vertebral fracture.

Associations Between Homocysteine, Bone Turnover, BMD, Mortality, and Fracture Risk in Elderly Women†

Homocysteine has been suggested to be a risk factor for fracture, but the causal relationship is not clear. In 996 women from the OPRA study, high homocysteine level was associated with high bone marker levels and low BMD at baseline. During a mean 7‐year follow‐up, high homocysteine level was associated with mortality, but no clear association to fracture risk existed.

Effect of fracture on bone turnover markers: A longitudinal study comparing marker levels before and after injury in 113 elderly women

In this longitudinal, prospective, and population‐based study (n = 1044), seven BTMs were assessed before and after trauma in 113 elderly women (85 with fractures). Markers were not altered in the immediate postfracture period but were clearly elevated during fracture repair. Recent fracture should thus be taken into account when markers are used in clinical practice.

Bone Turnover Markers and Prediction of Fracture: A Prospective Follow-Up Study of 1040 Elderly Women for a Mean of 9 Years

Osteoporosis is characterized by compromised bone mass and strength, predisposing to an increased risk of fracture. Increased bone metabolism has been suggested to be a risk factor for fracture. The aim of this study was to evaluate whether baseline bone turnover markers are associated with long‐term incidence of fracture in a population‐based sample of 1040 women who were 75 years old (Malmö OPRA study). Seven bone markers (S‐TRACP5b, S‐CTX‐I, S‐OC[1–49], S‐TotalOC, S‐cOC, S‐boneALP, and urinary osteocalcin) were measured at baseline and 1‐year follow‐up visit. During the mean follow‐up of 9.0 years (range 7.4–10.9), 363 women sustained at least one fracture of any type, including 116 hip fractures and 103 clinical vertebral fractures. High S‐TRACP5b and S‐CTX‐I levels were associated with increased risk of any fracture with hazard ratios [HRs (95% confidence interval)] of 1.16 (1.04–1.29) and 1.13 (1.01–1.27) per SD increase, respectively. They also were associated with increased risk of clinical vertebral fracture with HRs of 1.22 (1.01–1.48) and 1.32 (1.05–1.67), respectively. Markers were not associated with risk for hip fracture. Results were similar when we used resorption markers, including urinary osteocalcin, measured at the 1‐year visit or an average of the two measurements. The HRs were highest for any fracture in the beginning of the follow‐up period, 2.5 years from baseline. For vertebral fractures, the association was more pronounced and lasted for a longer period of time, at least for 5 years. In conclusion, elevated levels of S‐TRACP5b, S‐CTX‐I, and urinary osteocalcin are associated with increased fracture risk for up to a decade in elderly women.

X-Stop Versus Decompressive Surgery For Lumbar Neurogenic Intermittent Claudication: A Randomized Controlled Trial With 2 Years Follow-Up.

Study Design. Prospective randomized controlled study. Objective. To compare the outcome of indirect decompression by means of the X-Stop (Medtronics Inc., Minneapolis, MN) implant with conventional decompression in patients with neurogenic intermittent claudication due to lumbar spinal stenosis. Summary of Background Data. Decompression is currently the “gold standard” for lumbar spinal stenosis but is afflicted with complications and a certain number of dissatisfied patients. Interspinous implants have been on the market for more than 10 years, but no prospective study comparing its outcome with decompression has been performed. Methods. After power calculation, 100 patients were included: 50 in the X-Stop group and 50 in the decompression group. Patients with symptomatic 1- or 2-level lumbar spinal stenosis and neurogenic claudication relieved on flexion were included. X-Stop operations were performed under local anesthesia. The mean patient age was 69 (49–89) years, and the male/female distribution was 56/44. Minimal dural sac area was in all cases except two 80 mm2 or less. The noninferiority hypothesis included 6, 12, and 24 months of follow-up, and included. intention-to-treat as well as as-treated analyses. The primary outcome meansure was the Zürich Claudication Questionnaire, and the secondary outcome measures was the visual analogue scale pain, Short-Form 36 (SF-36), complications, and reoperations. Results. The primary and secondary outcome measures of patients in both groups improved significantly. The results were similar at 6, 12, and 24 months and at no time point could any statistical difference between the 2 types of surgery be identified. Three patients (6%) in the decompression group underwent further surgery, compared with 13 patients (26%) in the X-Stop group (P = 0.04). Results were identical in intention-to-treat and as-treated analyses. Conclusion. For spinal stenosis with neurogenic claudication, decompressive surgery as well as X-Stop are appropriate procedures. Similar results were achieved in both groups, however, with a higher number of reoperations in the X-Stop group. Patients having X-Stop removal and decompression experienced results similar to those randomized to primary decompression. Level of Evidence: 1

Effects of cigarette-smoking on bone mass as assessed by dual-energy X-ray absorptiometry and ultrasound.

Abstract: In order to elucidate the influence of nicotine smoking on bone mass in elderly women, bone mass was cross-sectionally assessed by dual energy X-ray absorptiometry (DXA) in total body, hip and lumbar spine, as well as with ultrasound of calcaneus and phalanges of the hand. Subjects were 1,042, 75-year old women, recruited on a population basis (Osteoporosis Prospective Risk Assessment (OPRA) study). We found bone mineral density (BMD) to be lower in hip (0.71 vs. 0.76 g/cm2, p<0.0001 for femoral neck) and total body (0.96 vs. 1.02 g/cm2, p<0.0001) in current smokers compared to never-smokers. There was no difference in BMD of the lumbar spine between current smokers and never-smokers. Bone mass as assessed by ultrasound of the calcaneus was lower for speed of sound (p<0.01), broadband ultrasound attenuation (p<0.0001) and stiffness (p<0.0001) in current smokers than in never-smokers. No differences were found for ultrasound measurements of the phalanges between smokers and never-smokers. Also, weight and current physical activity as assessed by a questionnaire differed significantly between current smokers and never-smokers. There was no evident difference between former smokers and never-smokers in any of the skeletal regions assessed by DXA or ultrasound. After correcting for differences in weight and physical activity, current smokers had lower BMD in all hip sites (p<0.05) and total body (p<0.01) compared to never-smokers. Ultrasound and BMD spine did not differ between these two groups after correction for weight and physical activity. We conclude that nicotine smoking has a negative influence on bone mass independent of differences in weight and physical activity. This difference is detected by DXA but not by ultrasound measurements of the calcaneus or the phalanges. The present data are encouraging since no bone mass differences were found between former and never-smokers.

Prediction of bone loss using biochemical markers of bone turnover

SummaryThe association between baseline levels of eleven bone turnover markers and 5-year rate of bone density change was prospectively studied in a population-based sample of 601 75-year-old women. Several bone formation and resorption markers as well as urinary osteocalcin were modestly correlated to rate of bone density change.IntroductionPrediction of bone loss by bone turnover markers (BTMs) has been investigated with conflicting results. There is limited information in the elderly.MethodsEleven bone turnover markers were analyzed in 75-year old women in the OPRA study (n = 601) and compared to the 5-year change of areal bone mineral density (aBMD) in seven skeletal regions.ResultsAnnual aBMD change varied between +0.4% (spine) and −2.0% (femoral neck). Significant associations (p < 0.01) were found for four different serum osteocalcins (S-OCs) (standardized regression coefficient −0.20 to −0.22), urinary deoxypyridinoline (−0.19), serum TRACP5b (−0.19), serum CTX-I (−0.21), two of the three urinary osteocalcins (U-OCs) (−0.16) and aBMD change of the leg region (derived from the total body measurement). After adjustment for baseline aBMD, associations were found for all S-OCs (−0.11 to −0.16), two of the three U-OCs (−0.14 to −0.16) and aBMD change at the total hip, and for three of the four S-OCs (−0.14 to −0.15), S-TRACP5b (−0.11), two of the three U-OCs (−0.14 to −0.15) and aBMD change at the femoral neck. There were no significant results concerning aBMD change at the spine.ConclusionThis study indicates that BTMs are correlated with aBMD loss in some skeletal regions in elderly women.

Influence of muscle strength, physical activity and weight on bone mass in a population-based sample of 1004 elderly women

High physical activity level has been associated with high bone mass and low fracture risk and is therefore recommended to reduce fractures in old age. The aim of this study was to estimate the effect of potentially modifiable variables, such as physical activity, muscle strength, muscle mass and weight, on bone mass in elderly women. The influence of isometric thigh muscle strength, self-estimated activity level, body composition and weight on bone mineral density (dual energy X-ray absorptiometry; DXA) in total body, hip and spine was investigated. Subjects were 1004 women, all 75 years old, taking part in the Malmö Osteoporosis Prospective Risk Assessment (OPRA) study. Physical activity and muscle strength accounted for 1–6% of the variability in bone mass, whereas weight, and its closely associated variables lean mass and fat mass, to a much greater extent explained the bone mass variability. We found current body weight to be the variable with the most substantial influence on the total variability in bone mass (15–32% depending on skeletal site) in a forward stepwise regression model. Our findings suggest that in elderly women, the major fracture-preventive effect of physical activity is unlikely to be mediated through increased bone mass. Retaining or even increasing body weight is likely to be beneficial to the skeleton, but an excess body weight increase may have negative effects on health. Nevertheless, training in elderly women may have advantages by improving balance, co-ordination and mobility and therefore decreasing the risk of fractures.

Single nucleotide polymorphisms in the human gene for osteoprotegerin are not related to bone mineral density or fracture in elderly women

Osteoprotegerin (OPG), a secreted member of the tumor necrosis factor receptor family, is a potent inhibitor of osteoclast activation and differentiation. In animal models OPG prevents bone loss, and in humans bone resorption can be reduced by injections of OPG. OPG may also play a role in cardiovascular disease since mice lacking the OPG gene display arterial calcification. In a screening effort of the OPG gene, we recently discovered a single nucleotide polymorphism in the promoter region of OPG (T950C), and reported an association with vascular morphology and function in 59 healthy individuals. Due to the pronounced effect of OPG on bone turnover, the present study was conducted to investigate whether OPG polymorphisms are also associated with bone mineral density or with fracture. The relationship between single nucleotide polymorphisms in the promoter region of OPG (T950C) and the first intron (C1217T), and bone mineral density, measured by DXA in the hip or spine or ultrasound of the heel, was investigated in the Malmö OPRA-study of 1044 women, all 75 years old. The possible relation to fracture incidence was also analyzed. Among the 858 and 864 individuals respectively, genotyped, no significant associations between the investigated single nucleotide polymorphisms and bone mineral density measurements (T950C P = 0.50–0.64, C1217T P = 0.51–1.00), quantitative ultrasound measurements of the calcaneus, or fractures (T950C P = 0.61–0.66, C1217T P = 0.14–0.33) were found. Thus, our results show that polymorphisms in the OPG gene, one of which has previously been found to be associated with cardiovascular morphology and function, are not associated with bone mineral density in elderly Swedish women.

Bone mineral density in old age: the influence of age at menarche and menopause

Being aware that age at menarche, age at menopause, and length of fertile period influence bone mineral density (BMD) in the early postmenopausal period, we have failed to find any earlier studies where such an influence on the axial skeleton has been studied in old age when the incidence of hip fracture starts to increase. A large cohort of women, all 75 years old (n = 1044) participated in the Malmö Osteoporosis Prospective Risk Assessment (OPRA) Study. The BMD of the lumbar spine and femoral neck was assessed by a dual-energy X-ray absorptiometry (DXA) technique. Age at menarche and at menopause was recalled with a questionnaire. Also, data on estrogen medication was collected. We found that, after excluding ever-users of potent estrogens (n = 49), there was a small but significant correlation of early menarcheal age with high BMD of the lumbar spine (r = −0.08; P = 0.017) and femoral neck (r = −0.10; P = 0.002) at age 75. Excluding the extremes (5% of the women) with very early or very late menarche, age at menarche no longer influenced the BMD in old age (r = −0.06; P = 0.113). Age at menopause had no influence on the BMD of the lumbar spine (r = 0.04; P = 0.246) or femoral neck (r = 0.00; P = 0.985), at age 75. The length of the fertile period did not influence BMD in old age. The influence of menarcheal or menopausal age on BMD at age 75 was not substantially altered after including body mass index (BMI) in a multiple regression model. Age at menarche or menopause seems to be of limited or no importance as a risk factor for osteoporosis when subjects are age 75 or older.