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At least 19 recordsLinked to original sources

PubMed1984

Studies of marginal zinc deprivation in rhesus monkeys. V. Fetal and infant skeletal effects.

Skeletal maturation was evaluated in newborn and infant rhesus monkeys that had been subjected to a marginally zinc-deficient diet (4 ppm zinc) from conception through 12 months of postnatal life. Serial radiographic assessment of skeletal development was performed and compared to both ad libitum and pair-fed controls. Radiographs were obtained at birth and at 1, 3, 9, and 12 months of age. In each age group a maturation indicator was selected to identify individuals with abnormal skeletal maturation defined on the basis of presence of epiphyseal ossification centers. Animals were compared only within a given sex group. Additionally, to evaluate endochondral bone mineralization, the appearance of the zone of provisional calcification on the metaphyseal side of the growth plate and the width of the growth plate were assessed. A marginal level of zinc deprivation during gestation and during the 1st yr of life was found to be associated with significantly delayed skeletal maturation and defective mineralization. This abnormality of bone mineralization has many features similar to human rachitic syndromes and suggests that zinc plays an important role in endochondral bone formation.

Animals↗

PubMed1995

An in-vivo model for the rapid assessment of skeletal effects of anabolic agents.

We recently developed an in vivo model which can be used to rapidly assess the local skeletal effects of anabolic agents. In this model, 160 g Sprague-Dawley (SD) rats were used. A stainless steel cannula was inserted into the marrow cavity of the proximal tibia through the anterior-medial cortex 6 mm distal to the knee joint. The outer opening of the cannula was covered by skin. Agents with known anabolic skeletal effects or vehicle were injected daily for 10 days into the marrow region by a small needle passing through the cannula. Rats were also injected subcutaneously with a fluorescent bone marker to label the newly formed bone. Injection sites were fixed, embedded, and sectioned for histomorphometric analysis of trabecular bone. PTH and PGE2 stimulated a large amount of new trabecular bone formation in regions proximal and distal to the injection site as measured by histomorphometry. Control groups showed minimal bone formation, limited to formation of a thin layer of bony shell immediately surrounding the cannula. The profound anabolic skeletal effects of PTH and PGE2 seen in this Local Injection Model are similar to those seen in systemic injection (i.e. subcutaneous injection in intact or castrated male and female rats) previously reported. This Local Injection Model combines numerous advantages of in vivo models (systemic injection) and in vitro models when assessing agents with anabolic skeletal activities. Compared to conventional in vivo systemic injection models, this model enables detection of anabolic skeletal effects using very small quantities (in microgram) of test agents in a short treatment period (< 10 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2003

Skeletal effects of cyclosporin A are gender related in rats.

The immunosuppressive drug cyclosporin A (CsA) is thought to be involved in the pathogenesis of posttransplantation osteoporosis. To evaluate further the skeletal effects of CsA, we treated aged male and female sham-operated and gonadectomized rats with low doses of CsA for 4 months. Here, we show that CsA is antiresorptive and bone-sparing in aged female rats but increases bone resorption and reduces bone mass in aged male rats. However, even in male rats, CsA treatment, at clinically relevant doses, increased bone resorption only transiently and did not result in pronounced long-term cancellous bone loss. The gender-specific skeletal effects of CsA were not modulated by sex hormones or gonadectomy. CsA did not influence sex steroid metabolism in male or female rats. However, endogenous estradiol in sham-operated female rats (and especially, exogenous administration of 17beta-estradiol in ovariectomized rats) markedly diminished blood levels of CsA, probably by increasing hepatic CsA metabolism. Although the mechanism for the gender-specific skeletal effects of CsA is still obscure, our findings may have important implications for clinical therapy with CsA.

Amino Acids↗

PubMed1996

A comparison of the skeletal effects of intermittent and continuous administration of calcitonin in ovariectomized rats.

The study was designed to compare the skeletal effects of intermittent and continuous administration of calcitonin (CT) in ovariectomized (OVX) rats. Female rats were sham operated or OVX at 3 months of age and treated for 6 weeks with vehicle or salmon CT. Sham-operated control rats were injected subcutaneously with vehicle on alternate days. One group of OVX rats was treated with vehicle intermittently by subcutaneous injection or continuously via Alzet osmotic minipumps. The remaining OVX rats were treated with CT by either subcutaneous injections (16 U/kg) on alternate days or by continuous infusion via minipumps at a daily dose of 8 U/kg. OVX rats treated with CT continuously were mildly hypocalcemic compared with all other groups. The proximal tibial metaphyses of vehicle-treated OVX rats were osteopenic with a cancellous bone volume at only 28% of the vehicle-treated control level. This bone loss was associated with increased indices of bone turnover such as osteoclast surface, osteoblast surface, and bone formation rate. Cancellous bone volume in OVX rats treated with CT either intermittently or continuously was significantly higher than that of vehicle-treated OVX rats, but lower than that of vehicle-treated control rats. Treatment of OVX rats with intermittent or continuous CT significantly decreased all indices of bone turnover compared with vehicle-treated OVX rats. However, osteoclast and osteoblast surfaces of OVX rats treated with CT continuously were still significantly higher than those of vehicle-treated control rats. These results indicate that intermittent and continuous administration of CT had similar skeletal effects in OVX rats. Both treatment regimens depressed bone turnover and partially prevented cancellous bone loss in the estrogen-deplete skeleton.

Analysis of Variance↗

PubMedDate not supplied

Metabolic and skeletal effects of low and high doses of calcium acetate in patients with preterminal chronic renal failure.

BACKGROUND: Secondary hyperparathyroidism commonly evolves, as the glomerular filtration rate falls. The metabolic and skeletal effects of a possible remedy, calcium acetate, have not been studied in patients with preterminal chronic renal failure. METHODS: Men with a mean creatinine clearance of approximately 30 ml/min took calcium acetate for 24 weeks at doses which provided 507 or 1,521 mg calcium/day with meals. Metabolic determinations were made at intervals of 4-8 weeks, and the bone mineral density (BMD) was measured at the beginning and at the end of the trial. RESULTS: The low-dose regimen produced no metabolic or skeletal effect. In subjects prescribed the high-dose regimen, the 24-hour urine phosphorus excretion fell from 0.53 mg/mg creatinine to values ranging from 0.34 to 0.41 mg/mg creatinine. The theoretical phosphorus threshold concentration rose by a maximum of 38.6%, and the serum phosphorus concentration did not change. The mean serum calcium concentration rose by a maximum of 7.2%. The mean fractional changes in parathyroid hormone and 1,25-dihydroxyvitamin D concentrations ranged from -27.0 to -39.6% and from -5.0 to -20.3%, respectively. The BMD increased at L1, L3, and L4. CONCLUSION: Calcium acetate prescribed to deliver 1,521 mg calcium/day with meals reduced parathyroid hormone and 1,25-dihydroxyvitamin D concentrations and increased lumbar BMD in men with preterminal chronic renal failure.

Acetates↗

PubMed1997

Skeletal effects of menstrual disturbances in athletes.

This article reviews the skeletal effects and clinical implications of menstrual disturbances in active women. At the lumbar spine, menstrual disturbances are associated with premature bone loss or failure to reach peak bone mass, while appendicular sites are less affected. This suggests that trabecular bone is more sensitive to hormonal stimuli and less responsive to mechanical loading than cortical bone. Although the mechanisms responsible for the detrimental effects of menstrual disturbances are likely to be multifactorial, low circulating levels of oestrogen are thought to be the main cause. The clinical significance of menstrual disturbances depends upon a number of factors, including type of sport, genetic background, body composition and calcium intake. Not all athletes who present with menstrual disturbances will develop osteopenia. Nevertheless, the risk of stress fracture does seem to be increased in athletes with menstrual disturbances and with lower bone density. Whether athletes with menstrual disturbances are at a greater risk for osteoporosis in later life is not yet known. Bone loss can be at least partially reversed, especially with the spontaneous resumption of menses. This may serve to offset any previous increased risk of osteoporosis. Furthermore, other factors, apart from low bone mass, act to determine the likelihood of osteoporotic fractures. Therefore, the clinical significance of menstrual disturbances associated with exercise participation needs to be established for each individual athlete. Bone densitometry may guide the clinician in this respect and assist in the formulation of appropriate management strategies.

Bone Density↗

PubMed1979

Skeletal effects of megavoltage irradiation in survivors of Wilms' tumor.

The skeletal effects of megavoltage irradiation (60Co) in 25 long term survivors of Wilms' tumor are described. In general, the changes seen with megavoltage irradiation are as frequent but not as severe as those previously reported after orthovoltage irradiation. Vertebral body changes generally occur within 5 years after irradiation. Scoliosis and/or kyphosis do not usually develop until after five years postirradiation. Kyphotic curves tend to progress after the adolescent growth spurt while scoliotic curves do not. Other bony and nonosseous changes are detailed.

Bone and Bones↗

PubMed1996

Ovarian status influences the skeletal effects of tamoxifen in adult rats.

Tamoxifen (TAM), an antiestrogen used in adjuvant therapy for breast cancer, is currently being evaluated for prevention of breast cancer in premenopausal and postmenopausal disease-free women. In light of this clinical application in young women, the skeleton's potential predisposition for osteoporosis following long-term treatment with an antiestrogen is a concern. In postmenopausal women being treated for breast cancer TAM was shown to prevent bone loss. There is little information, however, about the skeletal effects of TAM in premenopausal women. Previous animal studies in ovariectomized (OVX'd) rats have consistently reported TAM to prevent cancellous and cortical bone loss. The effects of TAM on ovary-intact animals, however, are not well established. We have performed a histomorphometric analysis in order to evaluate the influence of ovarian function on the skeletal effects of long-term TAM treatment in the laboratory animal model. Six-month-old rats were implanted subcutaneously with pellets designed for the controlled release of TAM at a dose (5 mg/3 wks) previously shown to be effective at antagonizing short-term bone loss in OVX'd growing rats. TAM acted as an estrogen agonist on cortical bone measurements in tibia of ovary-intact as well as OVX'd rats. In cancellous bone of OVX'd rats, TAM reduced indices of bone formation and resorption and reduced the bone loss from over 90 percent to less than 50 percent. In ovary-intact rats, however, TAM produced a 31 percent loss of cancellous bone, a deficit associated with a 26 percent reduction in the trabecular number. These results clearly demonstrate an interaction between TAM and ovarian status whereby TAM partially prevents estrogen-deficient bone loss in OVX'd animals but antagonizes selective actions of estrogen on the skeleton of ovary-intact animals.

Analysis of Variance↗

PubMed1989

A comparison of the skeletal effects of goserelin and danazol in premenopausal women with endometriosis.

The skeletal effects of two therapies for endometriosis that produce hypo-oestrogenism in 23 premenopausal women have been studied. Eleven women received goserelin 3.6 mg monthly by subcutaneous implant and 12 women received danazol 600 mg daily, orally, both for 6 months. Goserelin causes a small decline in spinal bone density, but a greater loss of density in the proximal femur. Preliminary results show no evidence that bone loss is reversible after stopping therapy. Danazol treatment is not associated with loss of bone. Prolonged or repeated courses of treatment with goserelin alone could lead to a clinically significant adverse effect on the skeleton.

Adult↗

PubMed1998

Skeletal effects of constant and terminated use of sodium risedronate in ovariectomized rats.

AIM: To study the skeletal effects of constant and terminated use of sodium risedronate (Ris) treatment in the ovariectomized (Ova) rats. METHODS: Ris 5 micrograms.kg-1, s.c., twice a wk. The proximal tibial metaphysis (PTM) were processed undecalcified for quantitive bone histomorphometry. RESULTS: (1) Placebo-treated (normal saline) Ova rats were characterized by decreased trabecular area (TA) on d 60, d 81, and d 150 compared with aging controls, and bone resorption was over formation with high bone turnover. (2) Ova rats were treated with Ris for 60, 81, and 150 d (Ris-on) increased. (TA 217%, 108%, and 101%) respectively, vs Ova rats and depressed bone turnover indices to aging control level, but bone mass did not maintain at high level in 150-d group as in the early stage. (3) Ova rats were pretreated with Ris for 60 d and then terminated (Ris-on/off), followed by sequential sacrifice of rats on 21 and 90 d. Withdrawal on 21 d showed the same results as the match-age Ris-on group. Withdrawal on 90 d still maintained cancellous bone mass at a high level vs 150 d Ris-on groups (+26%) and aging control group (+27%). CONCLUSION: Regimen of Ris 60 d on then 90 d off prevented the development of osteoporosis in Ova rats.

Animals↗

PubMed1999

Skeletal effects of constant and terminated use of risedronate on cortical bone in ovariectomized rats.

To study the skeletal effects of continual and terminated use of risedronate treatment on cortical bone in ovariectomized (Ovx) rats, we used risedronate (Ris), 5 microg x kg(-1), by subcutaneous injections, twice per week. The middle part of the tibial shafts (Tx) were processed undecalcified for quantitive bone histomorphometry. Cortical bone and the marrow areas of the tibial shaft did not change in either sham-Ovx or Ovx rats during the 150-day experimental period. Continued administration of Ris for 150 days decreased the marrow area and increased the percentage of cortical area compared with the matching sham and Ovx group. A decrease in bone formation indices in both periosteal and endocortical surfaces of Tx in sham-operated rats between the age of 5 and 8 months was seen. Ovariectomy increased the percentage of labeled perimeter in the periosteal area, and markedly increased the percentage of eroded perimeter in the endocortical surface compared with sham control groups in 81 and 150 days. Bone formation indices of Ris treatment were increased in periosteal surfaces, and percentages of eroded perimeter were decreased more in endocortical surfaces in 150 days than in the matching sham and Ovx groups. These data matched our static data, which showed a significantly increased percentage of cortical bone area and decreased percentage of marrow area. These bone gains were not maintained in the 90-day Ris withdrawal group. For cancellous bone, the 60-day Ris-treated high bone mass was maintained in the withdrawal group and not maintained in Ris continmuously treated group. These results indicate the effects of constant and terminated use of Ris in cortical bone were different from those in trabecular bone in the proximal tibial metaphysis.

Animals↗

PubMed1991

Skeletal effects of calcitonin in ovariectomized rats.

Although calcitonin (CT) has been shown to be effective for the prevention of bone loss in early postmenopausal women, the skeletal effects of the hormone specifically during the early stages of estrogen deficiency have not been characterized histomorphometrically to date. The current study involves use of the ovariectomized (OVX) rat as an animal model for early postmenopausal bone loss to perform such a histomorphometric analysis. One group of OVX rats was injected sc with salmon CT on alternate days for a 6-week period. Additional groups of OVX and sham-operated control rats were treated with vehicle alone. In comparison to control rats, the proximal tibia of vehicle-treated OVX rats were characterized by a 3-fold decrease in cancellous bone volume and significant increases in osteoblast surface (+200%), osteoclast surface (+143%), mineralizing surface (+111%), mineral apposition rate (+36%), bone formation rate (+181%), and longitudinal bone growth (+38%). In contrast, treatment of OVX rats with CT normalized tibial cancellous bone volume and significantly decreased all of the above cellular- and fluorochrome-based indices of bone turnover to near control levels. The results indicate that CT treatment depresses bone turnover and prevents the development of osteopenia in OVX rats. These findings are consistent with the bone protective effect of CT in early postmenopausal women and further support the OVX rat as an animal model for the preclinical evaluation of prophylactic treatments for postmenopausal bone loss.

Animals↗

PubMed1993

Skeletal effects of withdrawal of estrogen and diphosphonate treatment in ovariectomized rats.

The study was designed to determine the skeletal effects of withdrawal of estrogen and diphosphonate treatment in the estrogen-deplete state. Groups of ovariectomized (OVX) rats were treated with vehicle alone, estrogen, or the diphosphonates etidronate or risedronate for a 180-day period. A group of sham-operated control rats was treated for 180 days with vehicle alone. All treatments were then terminated, followed by sequential sacrifice of rats at 0, 35, 90, 180, and 360 days after withdrawal of treatment. The proximal tibia from each animal was processed undecalcified for quantitative bone histomorphometry. At the end of the treatment period, vehicle-treated OVX rats were characterized by cancellous osteopenia and increased bone turnover relative to vehicle-treated control rats. Treatment of OVX rats with estrogen or diphosphonates depressed bone turnover and protected against cancellous osteopenia. During the withdrawal period, OVX rats previously treated with estrogen exhibited rapid bone loss associated with increased bone turnover. The bone protective effect of the hormone in OVX rats was nearly completely lost by 90 days of withdrawal. In contrast, OVX rats maintained low levels of bone turnover and normal cancellous bone mass at 180 days of withdrawal from diphosphonate treatment. The results suggest that estrogen-deplete women who are withdrawn from estrogen replacement are at high risk for subsequent bone loss. They further suggest that widely spaced periods of intermittent diphosphonate treatment may be sufficient to prevent the development of osteopenia in postmenopausal and oophorectomized women.

Animals↗

PubMed1998

Skeletal effects of low-dose cyclosporin A in aged male rats: lack of relationship to serum testosterone levels.

The aim of this study was to investigate the skeletal effects of cyclosporin A (CsA) in a dose range relevant to clinical medicine in lumbar vertebral cancellous bone of aged male rats and to correlate these effects with possible changes in serum testosterone levels. Thirty-one 18-month-old male Wistar rats were divided into four weight-matched groups and subcutaneously injected with either 0, 1, 3, or 5 mg of CsA/kg of body weight three times per week After 4 weeks of treatment, all rats were killed after in vivo fluorochrome labeling and the first lumbar vertebrae analyzed by quantitative histomorphometry. Serum was analyzed for total calcium, creatinine, alkaline phosphatase, osteocalcin, parathyroid hormone, total testosterone, and CsA levels. CsA administration resulted in a dose-dependent increase in serum osteocalcin levels and in histomorphometric indices of cancellous bone turnover in the axial skeleton. Furthermore, CsA-treated rats showed a deterioration of vertebral cancellous bone structure with increased discontinuity of the trabecular bone network due to trabecular plate perforations. Serum testosterone levels were not significantly changed by CsA treatment and were uncorrelated to all biochemical or histomorphometric indices of bone turnover. We conclude that the 4-week administration of CsA at doses that are close to those used in transplantation patients induced high turnover osteopenia in the axial skeleton of aged, 18-month-old male rats, and that these effects were likely not mediated by changes in serum testosterone levels.

Aging↗

PubMed1981

The long-term skeletal effects of EHDP in dogs.

Disodium hydroxymethanediphosphonic acid was administered subcutaneously (s.c.) to adult beagle dogs for 1 to 2 years at various dose levels to determine its skeletal effects when given chronically. The effects were followed densitometrically, radiographically and by making histomorphometric measurements in sequential rib biopsies. At low doses (0.1 and 0.5 mg/kg/day s.c.) EHDP caused a time-and-dose dependent reduction in the percentage of bone surfaces with active mineralization, a reduction in mineralization rates, a reduction in resorption spaces but no changes in osteoid seam widths. No treatment related bone fractures were noted at the 0.1 mg/kg/day level, while at 0.5 mg/kg/day, fracture incidence appeared slightly increased. At higher doses (2-10 mg/kg/day), there was also a reduction in the number of resorption spaces, but mineralization activity was totally blocked, osteoid seams became thickened and fracture incidence was markedly increased. In one group of animals, EHDP treatment was discontinued after one year of dosage at 5 mg/kg/day given subcutaneously. In these animals, mineralization activity reappeared within 3 months, but osteoid seams remained thickened until 7 months post-treatment. These data indicate that EHDP can have profound effects on bone remodeling in the dog but that these effects are dose-and-time-dependent and they appear to be reversible.

Animals↗

PubMed2000

Skeletal effects of estrogen deficiency as induced by an aromatase inhibitor in an aged male rat model.

Aromatization of androgens into estrogens may be important for maintenance of the male skeleton. To address this hypothesis, we evaluated the skeletal effects of selective estrogen deficiency as induced by the aromatase inhibitor vorozole (Vor), with or without 17beta-estradiol (E(2)) administration (1.35 microg/day), in aged (12-month-old) male rats. A baseline group was killed at the start of the experiment (Base). The control group (Control), the group treated with vorozole alone (Vor), the group treated with E(2) alone (E(2)), or the group with a combination of both (Vor + E(2)) were killed 15 weeks later. Vorozole significantly increased serum testosterone (T) and reduced serum E(2) compared with Control. Body weight gain and serum insulin-like growth factor-I (IGF-I) were also lower in Vor, whereas significant weight loss and decrease of serum IGF-I occurred as a result of E(2) administration. Bone formation as assessed by serum osteocalcin was unaffected but osteoid surface in the proximal metaphysis of the tibia was increased in Vor-treated rats. Bone resorption as evaluated by urinary deoxypyridinoline excretion was increased in Vor. Biochemical parameters of bone turnover were reduced significantly in all E(2) treated rats. Premature closure of the growth plates and decreased osteoid and mineralizing surfaces were also observed in E(2) and Vor + E(2). Apparent bone density of lumbar vertebrae and femur, as measured by dual-energy X-ray absorptiometry (DXA), was significantly reduced in Vor. Vorozole decreased femoral bone density mainly in the distal femur (trabecular and cortical region). This decrease of bone density was not present in E(2) and Vor + E(2). Similar findings were observed when bone density was assessed by peripheral quantitative computed tomography (pQCT); that is, trabecular density of the distal femur, the proximal tibia, and the distal lumbar vertebra were all lower in Vor. This decrease in density was not observed in all E(2)-treated animals. In conclusion, administration of the aromatase inhibitor, vorozole, to aged male rats induces net trabecular bone loss in both the appendicular and axial skeleton, despite a concomitant increase in serum testosterone. E(2) administration is able to prevent this trabecular bone loss in vorozole-treated animals.

Aging↗

PubMed2001

Mechanisms by which high-dose estrogen therapy produces anabolic skeletal effects in postmenopausal women: role of locally produced growth factors.

Conventional hormone replacement therapy acts primarily by preserving bone, but cannot restore lost bone in women with established osteoporosis. Studies in rodents have shown that high doses of estrogens have anabolic skeletal effects, and recent observations in a group of women treated long term with high doses of estrogen indicated that similar effects occur in humans. This study examines the hypothesis that locally produced growth factors, including transforming growth factor-beta (TGF-beta) and platelet-derived growth factors (PDGFs), are involved in mediating the anabolic effects of high-dose estrogen. Transiliac-crest bone biopsies were taken from ten women, aged 52-67 years (mean 58 years), who had been treated with high-dose estrogen for 15 years. Control samples were obtained from four age-matched postmenopausal women not receiving estrogen therapy. TGF-betas and PDGFs were analyzed for mRNA and protein expression by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Results showed both TGF-beta1 and -beta2 mRNA, expressed as a ratio to GAPDH, were increased in the estrogen-treated group with an eightfold increase for TGF-beta1 (0.258 +/- 0.246 [mean +/- SD] vs. 0.032 +/- 0.053 in the control group, p = 0.02) and a twofold increase for TGF-beta2 (p = n.s.). TGF-beta3 analysis showed only negligible amounts in both groups. Protein expression levels for TGF-beta1, -beta2, -betaRI and -RII were higher in the estrogen-treated group than in controls, the most marked effects being seen for TGF-beta1. PDGF-A protein expression was also significantly higher in osteoblasts and osteocytes in women treated with estrogen, whereas PDGF-B showed only modest differences. The percentage of bone surface occupied by osteoclasts, as determined by tartrate-resistant acid phosphatase (TRAP) staining, was significantly reduced in the estrogen-treated group (p = 0.001). These results demonstrate that high-dose estrogen therapy is associated with increased TGF-beta, TGF-betaR, and PDGF synthesis and decreased osteoclast activity, consistent with the hypothesis that these growth factors may mediate the actions of estrogen in bone.

Acid Phosphatase↗

PubMed1982

Skeletal effects of orthovoltage and megavoltage therapy following treatment of nephroblastoma.

A review of 19 patients treated for nephroblastoma between 1945 and 1978 by nephrectomy and radiotherapy with chemotherapy showed a marked improvement in cure rate in recent years. In the decade from 1950 to 1960 there are four survivors. From 1960 to 1970, there are nine survivors from 25 cases and since 1970 there are 19 survivors from 27 cases. Skeletal effects of radiation therapy have been reviewed in 22 patients--seven of whom had orthovoltage and 15 megavoltage therapy. Similar skeletal changes followed both orthovoltage and megavoltage therapy, being more severe after the adolescent growth spurt and when the follow-up was longer. The radiation dose was normally 3000 cGy and skeletal changes followed the lowest dose of 2200 cGY. Scoliosis of the lumbar spine, concave to the side of the tumour, with angulation ranging from less than 5 degrees to 54 degrees developed in 12 patients; all but one showed asymmetry of the body LV2. Kyphosis was present in three patients; anterior beaking of the vertebral body in 10; and 16 patients showed asymmetry of more than one vertebral body. Iliac hypoplasia was present in 19 patients, being unilateral when only the renal bed was irradiated. Analysis of the radiological changes expressed as a total score against the age at follow-up shows that severe changes follow orthovoltage therapy. It is too early to assess the full extent of megavoltage therapy simply because patients have not been followed up for a comparable length of time.

Adolescent↗