Bone turnover markers are correlated with quantitative ultrasound of the calcaneus: 5-year longitudinal data.

SUMMARY: Associations between bone turnover markers and calcaneal ultrasound (quantitative ultrasound, QUS) were studied in a population-based sample of 810 elderly women. Baseline bone turnover markers correlated with baseline QUS as well as with 5-year prospective changes in QUS. INTRODUCTION: Bone turnover markers are associated with areal bone mineral density, but the knowledge on the association with QUS is limited. METHODS: Eight hundred ten women, all 75 years old, were investigated at baseline. Five hundred six completed a 5-year follow-up. Bone turnover markers and calcaneal QUS [speed of sound (SoS), broadband ultrasound attenuation (BUA), stiffness] were investigated at baseline. QUS was investigated at follow-up. RESULTS: All bone turnover markers were correlated with baseline QUS [standardized regression (Beta(std)) values from -0.07, p < 0.05 to -0.23, p < 0.001], with the exception of bone-specific alkaline phosphatase (S-Bone ALP) which was not correlated with BUA and stiffness index. When the correlations between baseline bone turnover markers and 5-year changes in QUS were analyzed, three serum osteocalcins were correlated with changes of SoS and stiffness index (Beta(std) = -0.11, p < 0.05 to -0.17, p < 0.001). Also S-CTX-I correlated with changes of SoS and stiffness index (Beta(std) = -0.10 and -0.09, respectively, p < 0.05). S-TRACP5b, urinary deoxypyridinoline/crea, and U-MidOC/crea correlated with changes of SoS (Beta(std) = -0.10 and p < 0.05 for all). S-Bone ALP did not correlate with change of QUS. None of the bone turnover markers correlated with changes of BUA. CONCLUSIONS: Bone turnover markers correlate with concomitantly assessed QUS as well as with longitudinal change in QUS.

Genetic variation in the PTH pathway and bone phenotypes in elderly women: evaluation of PTH, PTHLH, PTHR1 and PTHR2 genes.

INTRODUCTION: Parathyroid hormone (PTH) is a key regulator of calcium metabolism. Parathyroid hormone-like hormone (PTHrP) contributes to skeletal development through regulation of chondrocyte proliferation and differentiation during early bone growth. Both PTH and PTHrP act through the same receptor (PTHR1). A second receptor, PTHR2, has been identified although its function is comparatively unknown. PTH hyper-secretion induces bone resorption, whereas intermittent injection of PTH increases bone mass. To explore the effects of genetic variation in the PTH pathway, we have analysed variations in PTH, PTHLH, PTHR1 and PTHR2 in relation to bone mass and fracture incidence in elderly women. MATERIALS AND METHODS: This study includes 1044 elderly women, all 75 years old, from the Malmö Osteoporosis Prospective Risk Assessment study (OPRA). Single nucleotide polymorphisms (SNPs) from 4 genes and derived haplotypes in the PTH signaling pathway were analysed in 745-1005 women; 6 SNPs in the PTH gene and 3 SNPs each in the PTHLH, PTHR1 and PTHR2 genes were investigated in relation to BMD (assessed at baseline), fracture (434 prevalent fractures of all types over lifetime, self-reported and 174 incident fractures up to 7 years, X-ray verified) and serum PTH. RESULTS AND CONCLUSION: Individually, SNPs in the 4 loci did not show any significant association with BMD. Neither were PTHLH, PTHR1 and PTHR2 polymorphisms associated with fracture. Three of 5 common haplotypes, accounting for >98% of alleles at the PTH locus, were identified as independent predictors of fracture. Haplotype 9 (19%) was suggestive of an association with fractures of any type sustained during lifetime (p=0.018), with carriers of one or more copies of the haplotype having the lowest incidence (p=0.006). Haplotypes 1 (13%) and 5 (37%) and 9 were suggestive of an association with fractures sustained between 50 and 75 years (p=0.02, p=0.013 and p=0.034). Carriers of haplotypes 1 and 5 were more likely to suffer a fracture (haplotype 1, p=0.045; haplotype 5, p=0.008). We conclude, that while further genotyping across the gene is recommended, in this cohort of elderly Swedish women, polymorphisms in PTH may contribute to the risk of fracture through mechanisms that are independent of BMD.

The proportion of carboxylated to total or intact osteocalcin in serum discriminates warfarin-treated patients from control subjects.

We assessed the serum concentration of gamma-carboxylated osteocalcin (OC), total OC, and full-length OC in a clinical setting of 37 patients on continuous warfarin treatment (international normalized ratio 2.0-3.8). A comparison was done with the results from 30 untreated age-matched controls. Four monoclonal antibodies, previously generated and characterized as to their ability to recognize different human OC forms and fragments, were used in three two-site immunofluorometric assays. The warfarin-treated patients had significantly lower levels of carboxylated OC 4.9 +/- 3.8 (+/- 1 SD) ng/ml compared with the controls 13.1 +/- 9.7 (p < 0.0001). There was no difference in the levels of total OC or full-length OC between the two groups of patients. A strong correlation was found between the serum concentration of carboxylated OC and total OC, both for the warfarin-treated patients (r = 0.98) and for the controls (r = 0.99). There was a distinct cut-off level at 0.80, in the quotient carboxylated OC/total OC, at which all warfarin-treated patients fell below and all controls above this level. Hence, the concentration or ratio of serum gamma-carboxylated OC in clinical settings such as warfarin-treated patients could be measured using two-site immunoassays.

Assessment of biochemical markers of bone metabolism in relation to the occurrence of fracture: a retrospective and prospective population-based study of women.

We have in a population-based setting evaluated biochemical markers of bone metabolism in 328 women, aged 40-80 years, and related it to contents of bone mineral measurements and the retrospective and prospective presence of fracture. The participants were recruited from the city population files. Serum samples for analysis of osteocalcin (Oc), procollagen I carboxy-terminal extension peptide (PICP), and carboxy-terminal telopeptide of type I collagen (ICTP) were taken, and forearm bone mineral content (BMC) was measured by single photon absorptiometry (SPA). Fracture history was recorded, and the information was verified and supplemented from both radiologic and orthopedic files. Five years later the registration of fractures was repeated. At the initial investigation, Oc was 23% lower in women who had sustained a fracture (n = 37) within 6 years before measurement (6.3 +/- 3.6 microgram/l vs 8.2 +/- 4.2 microgram/l (p = 0.006)), after adjusting for age and BMC difference. PICP and ICTP were not different from values in the women without fracture. However, in women aged 70-80 years with a fracture sustained during the previous 6 years, PICP was lower (128 +/- 32 microgram/l vs 144 +/- 34 microgram/l, p = 0.046). Oc and ICTP were significantly correlated to age and BMC (Oc-age r = 0.36, Oc-BMC r = -0.31, ICTP-age r = 0.44, ICTP-BMC r = -0.24). The correlations of PICP were weaker. Prospectively, logistic regression gave an odds ratio (OR) of 1.8 (p = 0.015) for a low PICP and fracture susceptibility, at a change of 1 SD, independent of age and BMC. In the age bracket 70-80, the odds ratio was 2.4 (p = 0.036). The odds ratio for ICTP, independent of age and BMC, was 1.9 (P = 0.043) for 1 SD decrease and subsequent fracture risk. We concluded that women who had sustained at least one recent fracture had an altered bone turnover with decreased bone formation but an unaltered resorption. Women with retrospectively registered fractures also sustained subsequent fractures. A decrease from the mean of the collagen markers PICP and ICTP was associated with an increased risk for future fracture. Utilizing these biochemical markers of bone metabolism in a female population, PICP and ICTP had a similar influence on the risk of future fracture as forearm BMC (OR = 1.6, p = 0.03).

Muscle contraction increases the in vivo structural strength to the same degree in osteopenic and normal rat tibiae.

The increase in structural capacity due to muscle contraction in the lower leg was investigated in osteopenic and normal rats. Osteopenia was induced by ovariectomy combined with a low-calcium diet (0.01%). The control rats were sham operated and fed a diet containing 1.1% calcium. After 7 weeks the right lower leg of all animals were fractured in three-point ventral cantilever bending during muscle contraction induced by electrical stimulation of the ischiatic nerve. The left tibiae were resected and fractured as each animal's control. During muscle contraction in vivo, the ultimate bending moment, energy absorption, bending stiffness, and deflection were significantly lower in the osteopenic than in the sham-operated animals. However, the increase in mechanical parameters due to muscle contraction comparing the in vivo and resected tibiae in each animal were equally high in the osteopenic and sham-operated animals. Ultimate bending moment in the resected tibiae was 10% higher in the sham-operated animals compared with the ovariectomized, proving mechanically weaker tibiae in the osteopenic rats. In accordance with this, the medullary area of the osteopenic rats was 46% larger in the distal tibial diaphysis, and the ultimate stress the tibiae could withstand was 15% lower in the osteopenic compared with the sham-operated rats. The trabecular bone volume in the distal tibial metaphysis of the osteopenic rats was reduced by 70% compared with the sham operated. This study shows that muscle protection against fracture can be substantial in osteopenic tibia and that it is of the same magnitude as in rats with normal bone mass.

Serum osteocalcin increases during fracture healing in elderly women with hip fracture.

The purpose of this study was to define the bone metabolic properties during the postfracture period in elderly women with hip fracture. Osteocalcin (Oc), a marker of bone formation, was measured in 58 women with hip fracture (77 +/- 7 years) admitted to the hospital from their own homes. Serum samples were taken on average 5 h (range 1-21) from fracture and at follow-up, on average 4.6 months later. Comparison was made with 58 age-matched (79 +/- 5 years) women. Women with hip fracture had initially 30% lower Oc levels compared to the controls (p = 0.0001). The Oc level was independent of time elapsed from trauma, within 18 h, after which the level further decreased. At follow-up, Oc showed a 44% increase (p = 0.0001) and had reached the level of the controls, but not beyond it. A concomitant, but less marked increase was noted for alkaline phosphatase (ALP) (p = 0.0001). We conclude that although the bone formation, as assessed by Oc, is apparently lower in elderly women who sustain a hip fracture, the ability to induce a fracture response, with an increased bone turnover during fracture healing is intact. Subsequently, it is essential that a time perspective is applied, as the bone metabolic changes in patients having sustained a fracture are related to the time elapsed from fracture.

Changes of bone mineral mass and soft tissue composition after hip fracture.

The aim of this prospective longitudinal study was to measure prospectively the bone mineral density (BMD) and anthropometric variables after a hip fracture. In particular, we studied changes in the BMD in both the injured and uninjured hips, and examined if the postoperative mortality rate and complications, including pseudarthrosis of the fracture and late segmental collapse of the head of the femur, could be predicted by early bone mass measurements. The bone mineral density and the body composition were measured with dual energy X-ray absorptiometry in 102 consecutive hip fracture patients, 31 men and 71 women, with a mean age of 74 and 79 years, respectively. All cases were operated on within 3 days. The measurements were undertaken within 10 days after the fracture, after 4 and after 12 months. The BMD of the hip fracture cases decreased, especially in the lower extremities where the patients lost 7%, during the first year after the fracture. The patients also lost lean body mass (5%) but gained fat (11%) during the same period. They lost significantly more bone mass in the fractured hip than in the uninjured hip (p < 0.05). No difference was found between those patients who survived and those who died within 2 years after their hip fracture in neither the initial measurement nor in the follow-up measurements. Also, we found no difference between those patients whose hip fracture healed and those who developed late segmental collapse or pseudarthrosis. In conclusion, osteoporotic hip fracture cases lose bone mass at an increased rate, especially in the fractured hip. Also, their soft tissue composition changes, gaining fat while losing muscle mass. Furthermore, it seems that early bone mineral measurements cannot predict postoperative failures or postoperative mortality.

Femoral neck geometry and radiographic signs of osteoporosis as predictors of hip fracture.

A total of 125 consecutive hip fracture patients were investigated regarding hip geometry. There were 33 men of mean age 76 +/- 10 years, and 92 women of mean age 78 +/- 9 years. Patients with previous hip surgery were excluded. Hip geometry (hip-axis length, width of collum femoris, and femoral shaft and neck-shaft angle) were registered on both plain radiographs and DEXA scans performed within 2 weeks after fracture. On the radiographs, the calcar femorale, the Singh index, and the femoral neck index (FNI) were also calculated and compared with earlier published values of bone mineral density hip in the hip fracture patients. The fracture cases were compared with controls, 192 DEXA scans and 163 radiographs, in patients without hip surgery or known hip disease. As measured on the DEXA scans we found a wider collum femoris and a wider femoral shaft in both the male and female fracture cases, compared to controls. Also, the fracture cases showed signs of osteoporosis as measured by the calcar femorale, the Singh index, and the femoral neck index. These measurements showed good correlation with bone mineral density of the hip as measured by the DEXA scans.

Age, gender, and fragility fractures are associated with differences in quantitative ultrasound independent of bone mineral density.

Bone strength is determined by bone mineral density (BMD) and bone structure. Dual-energy X-ray absorptiometry (DXA) measures BMD. Whether quantitative ultrasound (qUS) measures a property of bone distinct from BMD is uncertain. To evaluate this, DXA and qUS were measured in 58 fracture patients and 428 controls. To study the independent effects of age and gender on qUS measurements and control for BMD by study design rather than statistical methods, subgroups from the normative database were created and intentionally matched by the same femoral neck (FN) BMD. Speed of sound (SOS; m/sec), broadband ultrasound attenuation (BUA; dB/MHz), and stiffness index (SI) were then compared in individuals matched by FN BMD but differing in age, gender, and presence or absence of fractures. The results are presented as percentage difference (mean +/- SD). Elderly women with the same FN BMD as young women had 1 +/- 2% lower SOS (p < 0.05), 8 +/- 15% lower SI (p < 0.05), and 4 +/- 9% lower BUA (p = 0.07). Elderly women with the same FN BMD as elderly men had 5 +/- 9% lower BUA (p < 0.05). Elderly men with the same FN BMD as young men had 1 +/- 2% lower SOS (p = 0.1), 5 +/- 14% lower SI (p = 0.2), and 1 +/- 9% lower BUA (n.s.). Young women with the same FN BMD as young men had 2 +/- 7% lower BUA (n.s.). Women with fragility fractures had 8 +/- 11% lower BUA (p < 0.001) and 13 +/- 22% lower SI (p < 0.01) than controls with no fractures matched by FN BMD, age, and gender. Men with fragility fractures had 13 +/- 12% lower BUA (p < 0.01) and 16 +/- 19% lower SI (p < 0.05) than controls with no fractures matched by FN BMD, age, and gender. Despite comparable femoral neck BMD, qUS measurements differed according to age, gender, and fracture status, suggesting that qUS may provide additional information independent of femoral neck BMD, such as differences in connectivity or other properties yet to be identified.

Bone mineral mass in hip fracture patients.

The aims of this study were to measure the bone mineral density (BMD) and some anthropometric variables in patients with hip fracture, to compare these data with those from controls, and to compare the fractured and unfractured hip. Bone mineral measurements with dual energy X-ray absorptiometry (DEXA) were undertaken in 93 consecutive hip fracture patients, 26 men and 67 women, with a mean age of 75 and 78 years, respectively, within 10 days after injury. We found lower BMD in most measurements in both men and women compared with age- and sex-matched controls. The body weight and lean body mass were also significantly lower in the male hip fracture patients; in women only weight was lower. In women there was lower BMD in spine and hip in those who had sustained trochanteric hip fractures compared with those with cervical fracture. No such difference was found in men. There was no difference in BMD in the hip when patients with stable and unstable fractures were compared. In the fractured and nonfractured hips we measured BMD in regions of interest. In women with trochanteric hip fractures the BMD was decreased in the fractured hip compared with the uninjured. No such difference was found for cervical fractures or in men.

Balance and gait performance in an urban and a rural population.

OBJECTIVE: To compare the differences in standing balance and gait performance between two populations, correlated with age and physical activities of daily living. DESIGN: A cross-sectional study. SETTINGS: Malmö, the third largest city in Sweden, and Sjöbo, a typical agricultural community 60 km east of Malmö. PARTICIPANTS: Participants were 570 men and women from the urban community (urban) and 391 from the rural community (rural), born in 1938, 1928, 1918, and 1908, and women born in 1948. The two cohorts were subdivided into true urbans, who had lived only in the city (n = 269), and true rurals, who had never lived in a city (n = 354). MEASUREMENTS: Information about workload, housing, spare time activities, medication, and illness during different decades of life was gathered using two questionnaires. The first questionnaire was sent to the home after agreement to participate, and the second was presented at the test session. The clinical measurements were standing balance, gait speed, and step length. RESULTS: The urban subjects had significantly (P < .001) impaired balance compared with rural subjects. This difference increased with increasing age. The urban subjects walked faster than the rural subjects (P < .001), and the urban subjects used fewer steps than their rural counterparts (P < .001). Spare time activities had a significant influence on the above tests, but, except for gait velocity (P = .011), workload was of minor importance according to analysis of covariance. CONCLUSION: Background factors such as usual daily activities of living and lifestyle seem to be of importance when evaluating and comparing different populations with respect to their balance and gait performance.

Migration of the Charnley stem in rheumatoid arthritis and osteoarthritis. A roentgen stereophotogrammetric study.

Migration of 65 Charnley stems implanted with modern cementing techniques was studied by roentgen stereophotogrammetry. There were 25 patients with rheumatoid arthritis (RA) and 40 with osteoarthritis (OA) followed up for two years. In 43 cases a bone sample for histomorphometric analysis was obtained from the femur during the operation. In 22 cases the mean subsidence of the prosthetic head was 0.40 mm and in 20 the mean posterior migration was 1.25 mm. There was no difference in migration between the two diagnostic groups (p = 0.8) after adjusting for variations in gender, age and weight. Male gender was associated with increased subsidence (p = 0.006). Histological examination showed that the RA series had more osteoid surface (p = 0.04), but neither this, nor any of the other histomorphometric variables, influenced migration. These results suggest that, unlike the acetabular socket, the cemented Charnley femoral component is equally secure in osteoarthritis and in rheumatoid arthritis, and that its initial fixation is not influenced by the quality of the local cancellous bone. Our results provide data with which the early performance of new prosthetic designs and fixation methods can be compared.

Survival of hemiarthroplasties after cervical hip fractures.

The survivorship of 434 hemiarthroplasties implanted between 1969 and 1982 was calculated from modified life tables. Nine years after surgery 15% of the endoprostheses had been exchanged to a total hip prosthesis. The risk for such a revision was greatest during the first years. Only one of 51 cemented endoprostheses had to be exchanged. The age of the patients at the hemiarthroplasty averaged 76 years. Within 5 years after surgery 50% of the patients were deceased.

Prediction of bone loss using biochemical markers of bone turnover.

UNLABELLED: The 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. INTRODUCTION: Prediction of bone loss by bone turnover markers (BTMs) has been investigated with conflicting results. There is limited information in the elderly. METHODS: Eleven 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. RESULTS: Annual 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. CONCLUSION: This study indicates that BTMs are correlated with aBMD loss in some skeletal regions in elderly women.

Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women.

Vitamin D supplements have been used to prevent fractures. The effect may be mediated through increased bone mass, but also through reduced falling propensity. The aim of this study was to evaluate the association between 25-hydroxy vitamin D levels (25OHD), fall-associated variables (including tests of functional performance), and fracture in ambulatory women. At baseline 25OHD was measured in 986 women. Fall-associated variables were investigated at baseline. Fractures were recorded during a 3-year follow-up. Four percent of the women had 25OHD levels below 20 ng/ml (50 nmol/l), and 26% had 25OHD levels below 30 ng/ml (75 nmol/l). 25OHD correlated with gait speed (r =0.17, P <0.001), the Romberg balance test (r =0.14, P <0.001), self-estimated activity level (r =0.15, P <0.001), and thigh muscle strength (r =0.08, P =0.02). During the 3-year follow-up, 119 out of the 986 women sustained at least one fracture. The Cox proportional hazard ratio (HR) (95% confidence interval) for sustaining a fracture during the follow-up was 2.04 (1.04-4.04) for the group of women with 25OHD below 20 ng/ml, in which 9 out of 43 women sustained a fracture. Thirty-two of the 256 women with 25OHD levels below 30 ng/ml sustained a fracture during the follow-up, with a non-significant HR of 1.07 (1.07-1.61). This cohort of elderly, ambulatory women had a high mean 25OHD. A low 25OHD was associated with inferior physical activity level, gait speed and balance. A 25OHD level below 30 ng/ml was not associated with an increased risk of fractures in this study. However, a subgroup of women with 25OHD levels below 20 ng/ml had a tendency to an increased risk of fractures, which may be associated with an inferior physical activity and postural stability.

Tetracycline double-labelling in post-traumatic osteopenia in man.

Biopsy specimens were taken from parts of earlier fractured bones in seven patients with post-traumatic osteopenia and one healthy volunteer, who were all administered a double dose of tetracycline for the purpose of prelabelling. In the volunteer, specimens were taken from both the proximal tibia epiphysis and the iliac crest. The fraction of labelled surfaces and the rate of apposition were calculated. The results were also compared with normative data from the iliac crest. At least in the first year after fracture, post-traumatic osteopenia appears to be a condition with an increased appositional activity.

Trabecular bone changes in the greater trochanter after fracture of the femoral neck.

Bone samples were taken from the trabecular part of the greater trochanter in 32 patients who had a fracture of the ipsilateral femoral neck, and from 24 patients who had coxarthrosis. 42 cadavers served as controls. The samples were sectioned, stained and examined histologically. The coxarthrosis cases differed only slightly from normal, whereas the fracture cases had increased osteoid volume and surface. Osteoclasts were also increased in number, as were active osteoblasts.

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

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.

What is the impact of osteoporosis?

A body of evidence points towards a close connection between susceptibility to fractures and osteoporosis. The incidence of osteoporotic fractures, both in absolute figures and in age-specific figures, has increased worldwide throughout this century. Although some reports show that the age-specific incidence is levelling-off, there will be a continuously increasing number of individuals with such fractures that will have implications from an economical point of view not only for the affected individual but for society as a whole. The outcome after such fractures, especially those of the hip, is by no means always favourable, partly due to insufficient results after orthopaedic treatment and partly due to an already high comorbidity. Therefore, trying to prevent osteoporotic fractures by non-pharmacological or pharmacological regimens is of utmost importance.

Histomorphologic changes in the tibial epiphysis after diaphyseal fracture.

The amount of osteoid tissue, osteoclasts, and active osteoblasts was measured in biopsy specimens from the proximal end of the tibia in 20 patients who had sustained tibial shaft fractures. As compared with samples from 42 control subjects without fractures, there was a vast increase in the amount of osteoid tissue. The histologic appearance deviated from that of other skeletal conditions in that poorly calcified (osteoid) layers were found throughout the trabeculae, which, in some instances, were completely osteoid. The frequency of active osteoblasts (corrected for osteoid) was not increased in the patients with fractures, whereas osteoclasts were noted four times more frequently.