P. Lips

A fifteen-year longitudinal study in young adults on the relation of physical activity and fitness with the development of the bone mass: the Amsterdam Growth and Health Longitudinal Study

Although positive effects of physical activity are often reported, there are still uncertainties about the type, intensity, duration, and frequency of these activities that are most effective for (re)modeling bone mass during youth. In the Amsterdam Growth and Health Longitudinal Study, daily physical activity and fitness were monitored from age 13 to 29 years in a group of 182 males and females. At a mean age of 28 years, bone mineral density (BMD) was measured at three sites with dual X-ray absorptiometry (DXA): in the lumbar region (lumbar BMD), the femoral neck (hip BMD), and the distal radius (wrist BMD). Physical activity (PA) was estimated from a cross-check activity interview taking in consideration all daily physical activities during the last 3 months; PA was scored in two different ways: (1) metabolic physical activity score (METPA) by weighting the intensity (multiples of basic metabolic rate [METs]) and duration (minutes per week); and (2) mechanic physical activity score (MECHPA) by weighting the peak strain (ground reaction forces as multiples of body mass) irrespective of frequency and duration of the physical activities. Physical fitness was measured with a neuromotor fitness test (composite of six strength, flexibility, and speed tests) and as cardiopulmonary fitness (maximal oxygen uptake). The physical activity and fitness scores were calculated over two age periods: during adolescence (13-16 years) and during adulthood (21-27 years). The standardized regression coefficients (corrected for gender, biological age, body composition, and calcium intake) show that weight, physical activity (both METPA and MECHPA), and neuromotor fitness during adolescence and in young adulthood are significantly and positively related with the lumbar BMD (beta = 0. 11-0.40) and hip BMD (beta = 0.18-0.26), measured at the mean age of 28 years. This was not the case for cardiorespiratory fitness. No significant correlations at all are found with wrist BMD, a bone site that is less involved in physical activity and fitness. It can be concluded that daily physical activity during adolescence and in the young adult period is significantly related to the BMD at the lumbar spine and femoral neck at age 28 of males and females. Only neuromotor fitness and not cardiopulmonary fitness during adolescence and young adulthood is related to the BMD of males and females at age 28 years.

Biochemical parameters of bone turnover during ten days of bed rest and subsequent mobilization

Immobilization is associated with increased bone resorption. To investigate the early onset of increased bone resorption, we evaluated 14 patients who were immobilized for 10 days because of lumbar disc protrusion. The fasting urinary hydroxyproline/creatinine ratio increased significantly after four days (P less than 0.01), reached a peak after 10 days (16.4 +/- 3.3 mumol/mmol, 27.6 +/- 8.8 mumol mmol, P less than 0.01) and returned slowly to baseline values after mobilization. The fasting urinary calcium creatinine ratio followed a similar pattern. Serum calcium and phosphate increased during immobilization (P less than 0.01). Serum 1,25-dihydroxyvitamin D decreased significantly during immobilization (98 +/- 33 pmol/l vs. 79 +/- 36 pmol/l, P less than 0.05), and reached a nadir one week after mobilization (P less than 0.01). We conclude that there is an early significant increment in resorption parameters, with a slow return during the mobilization period. Serum 1,25-dihydroxyvitamin D is suppressed as a result of the increased serum calcium and serum phosphate levels.

Loss of bone in the proximal part of the femur following unstable fractures of the leg.

We evaluated the subsequent loss of bone from the proximal part of the ipsilateral and contralateral femora and from the lumbar spine of seven men and nine women who had a fracture of the tibia. The average age was sixty years. All of the fractures were unstable, and the involved leg bore no weight for an average of eight weeks. The bone mineral density was measured with dual-energy x-ray absorptiometry of the lumbar spine and of the femoral neck and the trochanteric region of both hips immediately after the fracture, after the period of immobilization, and at approximately three, six, and twelve months after the fracture. During the period of immobilization, the bone mineral density of the trochanteric region decreased an average of 9 +/- 7 per cent on the side of the fracture, compared with the value immediately after the fracture, but there was no change on the contralateral side (p < 0.01). At twelve months, the average decrease in the trochanteric area was 15 +/- 10 per cent on the side of the fracture, compared with the value immediately after the fracture, but again there had been no change on the uninjured side (p < 0.01). The bone mineral density of the femoral neck on the side of the fracture had decreased 6 +/- 6 per cent at twelve months, compared with a decrease of 2 +/- 4 per cent on the uninjured side (p < 0.05). The bone mineral density of the lumbar spine decreased only during the period of unloading of the fractured leg (1 +/- 2 per cent, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Additional weight-bearing during exercise is more important than duration of exercise for anabolic stimulus of bone: a study of running exercise in female rats

Mechanical loading is necessary for maintenance of skeletal integrity, but the most effective type, intensity, and duration of exercise are not known. In vivo experiments have indicated that the strain generated by the stimulus is more important than the duration of the stimulus. To elucidate this question, we studied 5-month-old female Wistar rats exercised on a motor-driven exercise belt for 17 weeks, 5 days per week (average velocity 20 m/min). Group 1 served as controls, group 2 was trained for 30 min, group 3 was trained for 30 min with a 50-g backpack, and group 4 was trained for 15 min with a 50-g backpack. Total body bone mineral content (BMC), bone mass of the lower extremities (LEBMC), total body lean soft-tissue mass (LSTM), and total body fat-tissue mass (FTM) were measured by dual-energy absorptiometry (DXA) at 0, 6, and 17 weeks. The BMC increased more in group 4 than in controls (15% vs. 8%, p < 0.03). In the other two intervention groups, no significant increases of total body BMC occurred compared with controls, although a trend was observed (12%). The LEBMC increased significantly in all exercising groups after 17 weeks, being 16% in group 2, 15% in group 3, and 20% in group 4, compared with 6% in controls (p < 0.05). The increase in LSTM after 6 weeks was most pronounced in group 3, at 20%, compared with 10% in the control group (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of Alendronate on Bone Mass After Distal Forearm Fracture

Fracture and immobilization of an extremity lead to bone loss at the fracture and at adjacent sites. We conducted a 1‐year, single‐center, prospective, randomized, double‐blind study to determine whether bone loss would occur in the distal radius after a Colles fracture and whether this loss could be prevented using an antiresorptive drug (alendronate). Thirty‐seven women with a recent fracture of the distal forearm and low bone mineral density (BMD) of the lumbar spine were randomized to receive either 10 mg alendronate daily or placebo. BMD of both forearms was measured at baseline and after 3, 6, and 12 months. The results of four women who developed reflex sympathetic dystrophy were not included in the analysis. In the placebo group, there was a significant reduction at 3 months and 6 months in BMD of total radius (p < 0.01), one‐third distal radius (p < 0.01), middistal radius (p < 0.05), and ultradistal radius (p < 0.01) on the fractured side. The loss in BMD at one‐third distal radius remained significant at month 12 (p ≤ 0.001). In the alendronate group BMD of total distal radius, one‐third distal radius, and middistal radius at the fractured side remained unchanged. BMD of ultradistal radius increased significantly at months 3, 6, and 12, compared with baseline (p < 0.05). The difference between the two treatment groups was significant at 3 months and 6 months and borderline significant (p = 0.054) after 1 year in total distal radius. In ultradistal radius the differences were significant at all time points. We conclude that BMD of the distal radius of a recently fractured forearm decreases significantly in the 6 months after fracture and the resulting deficit remains evident at least 1 year after fracture. This bone loss can be prevented by alendronate.

Long-term consequences of fracture of the lower leg: cross-sectional study and long-term longitudinal follow-up of bone mineral density in the hip after fracture of lower leg

The purpose of this study was to investigate whether bone loss in the hip, occurring after a fracture of the lower leg, persists many years after the fracture. In a long-term follow-up we measured bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) of both hips and the lumbar spine in a group of 11 patients, 5 years after a fracture of the lower leg. These patients were part of an earlier study, evaluating bone loss in the hip, up to 1 year after fracture of the lower leg. In this follow-up study, 5 years after fracture, loss from baseline BMD in the trochanteric region of the ipsilateral hip was 4.7% (p=0.04), whereas after a year in this group there was a decrease of 12.5% from baseline. On the contralateral side, hardly any change occurred. In the ipsilateral femoral neck, 5 years after fracture, BMD decreased by 2.9% (p=0.10), after 1 year loss from baseline was 5.1%. In a cross-sectional study we examined the differences in BMD of both hips, measured by DXA, in a group of 19 elderly patients reporting a fracture of the lower leg, with a mean time of 9.3 years after fracture. In this study, we found a 4.7% lower BMD in the trochanteric region of the hip on the fractured side compared with the nonfractured side (p=0.006), and a 2.9% lower BMD in the femoral neck (p=0.25). We conclude that, after fracture of the lower leg, BMD in the ipsilateral hip decreases significantly, with maximal bone loss after 1 year. After 5 years recovery has occurred, but not to baseline. Thereafter, significant excess bone loss is still observed in the trochanteric region. This persisting lower BMD may lead to an increased risk of another fracture in later years.

Transient osteoporosis and osteogenesis imperfecta. A case report.

The authors report migratory transient osteoporosis of the ipsilateral hip and ankle in a patient with osteogenesis imperfecta. The diagnosis was made with modern imaging techniques (magnetic resonance imaging, bone scintigraphy, and dual energy xray absorptiometry). Histologic examination after bone biopsy of the proximal femur showed possible microfractures. The treatment consisted of a regimen of nonweightbearing. One year after onset, the patient had no symptoms and no residual evidence of transient osteoporosis on radiographic studies. The etiology of transient osteoporosis in patients who have osteogenesis imperfecta is uncertain. The authors findings suggest that microfractures may play a role in the early pathophysiologic process.

Alendronate in the Prevention of Bone Loss After a Fracture of the Lower Leg

Fracture of a leg and the consequent absence from weight‐bearing lead to local bone loss. A 1‐year, single‐center, prospective, randomized, double‐blind study was conducted, to determine whether bone loss would occur in the proximal femur and the calcaneus after a fracture of the lower leg and whether this loss could be prevented by the antiresorptive drug bisphosphonate alendronate. Twenty‐three men and 18 women with a recent unstable fracture of the lower leg were randomized to receive either 10 mg of alendronate daily or placebo. Bone mineral density (BMD) of both hips and the lumbar spine was measured at baseline and 6 weeks and 3, 6, and 12 months after start of the treatment. Quantitative ultrasound (QUS) measurements of the calcaneus were performed at baseline on the noninjured side and at 6 weeks and 3, 6, and 12 months after start of treatment on both sides. After 1 year, in the placebo group, there was a significant decrease from baseline in BMD of the hip on the side of the fracture. In the alendronate group, there was no significant change from baseline. The differences in BMD between the two treatment groups on the side of the fracture were significant in all sites of the hip: 4.4% (p = 0.016) in the trochanter, 4.6% (p = 0.016) in the femoral neck, and 3.9% (p = 0.009) in the total hip. In the hip on the contralateral side, there were no significant changes from baseline in either treatment group and there was no difference between the two treatment groups. BMD in the lumbar spine increased in the alendronate group, and after 1 year there was a significant difference between the active treatment and placebo group of 3.4% (p = 0.04). One year after fracture, ultrasound parameters of the calcaneus in the placebo group were significantly lower on the fractured side compared with the contralateral side (p < 0.01). In the alendronate group, no significant difference between the two sides was observed. In conclusion, BMD of the proximal femur was still decreased 1 year after a fracture of the lower leg. Alendronate prevented this bone loss.

Effects of short-term low-dose heparin administration on biochemical parameters of bone turnover

Heparin therapy may cause osteoporosis. The effects of short-term low-dose heparin are not known. We have studied the effects of short-term heparin administration, twice daily 5000 IU s.c., for 10 days on the biochemical parameters of bone turnover in six healthy male volunteers. No effects were observed on the urinary excretion of hydroxyproline and calcium. Serum levels of cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), a new marker of bone resorption, did not change significantly. A slight but significant decrease in serum alkaline phosphatase was observed. TmP/GFR increased significantly during heparin administration. In all volunteers a uniform increase in serum transaminases appeared which completely reversed after discontinuation of heparin administration. We conclude that short-term low-dose heparin administration does not change biochemical parameters of bone resorption, but has a small significant suppressing effect on serum alkaline phosphatase levels. Heparin administration resulted in a significant but transient increase of serum transaminase levels.

Clonally Related But Phenotypically Divergent Human Cancer Cell Lines Derived from a Single Follicular Thyroid Cancer Recurrence (TT2609)

Starting from different regional samples taken from a heterogeneous follicular thyroid cancer recurrence in a male patient, a series of cell cultures was initiated. Three stable cancer cell lines were successfully established (TT2609-A02, TT2609-B02, and TT2609-C02) and kept in continuous culture for more than 3 years. The lines are each characterized by a unique set of biological parameters such as morphology, ploidy state, cell proliferation rate, ultrastructure, thyroid marker expression, p53 expression, karyogram, agar clonogenic capacity and tumorigenicity as xenografts in nude mice. These characterization studies point to a marked heterogeneity at the level of the clinical tumor recurrence. Karyotype analysis of the cell lines showed a pattern of aberrations indicating that the lines are clonally related and that the A02 and C02 lines are subsequently derived from the more original tumor cell type B02 after a tetraploidization event. It is concluded that the obtained cell lines represent an in vitro/in vivo model for human follicular thyroid cancer. The availability of a series of cell lines for human follicular thyroid cancer, mimicking the biological heterogeneity observed in patient tumors, enables both detailed fundamental investigation of thyroid cancer cell biology and the experimental exploration of new treatment approaches.