Bone mineral density in long-term survivors of childhood cancer.

Bone mineral density (BMD) of the lumbar spine was measured in 97 long-term survivors of childhood cancer 5-23 years after diagnosis using dual-energy X-ray absorptiometry (DXA). They had been treated for acute leukemia (n = 22), brain tumors (n = 16), lymphomas (n = 16), Wilms' tumor (n = 10), neuroblastoma (n = 7) and other cancers (n = 26). The correlations between BMD and the Z-scores for weight for height, height for age and weight for age at diagnosis and follow-up were evaluated with stepwise multiple regression. Correlations with cumulative corticosteroid and radiation dose were examined with Spearman's correlation coefficient. The number of nature of fractures were noted. A BMD Z-score of below -2 was present in 13 and a BMD Z-score of -1 to -2 in 31 children. In total, a low BMD was observed in 45% of children. Height for age at follow-up correlated significantly with BMD Z-score. Increasing doses of cranial irradiation (18-54 Gy) were associated with lower BMD (p = 0.001, Spearman). This was true also for 22 children with acute lymphoblastic leukemia (ALL) who had received 18-24 Gy cranial irradiation (p = 0.04, Spearman). Fractures occurred in 14 children following trauma. The difference in BMD Z-scores of children with and without fractures did not achieve statistical significance although the majority of the children with fractures had low BMD Z-scores. The significant inverse correlation between height for age at follow-up and BMD must be interpreted with the realization that DXA is not a volumetric measurement of BMD and that short stature is associated with a smaller skeletal mass.

Static bone histomorphometry in preterm and term babies.

The nature and pathophysiology of the bone loss which occurs in term and especially preterm neonates are poorly understood, and it is unclear whether this neonatal osteopenia results from impaired bone formation or increased bone resorption. This study compared the static bone histomorphometry of preterm and term babies, employing iliac crest bone biopsy specimens obtained postmortem. All the babies died within the first 6 days of life and none had any clinical, biochemical or radiologic evidence of metabolic bone disease. The trabecular bone volume, as well as static parameters of bone formation (OV/TV, OV/BV, OS/BS, OB.S/BS) did not differ significantly in preterm and term babies. Although time-spaced tetracycline labelling could not be employed in the present study, evidence of rickets was not apparent. Parameters of bone resorption in preterm babies were, however, significantly higher (p = 0.01) than those of term babies, suggesting that increased bone resorption and not impaired formation, underlies the development of osteopenia in the preterm neonate.

High turnover osteopenia in preterm babies.

Osteopenia is common in preterm babies, but its pathogenesis is uncertain. In this study bone density in babies was quantitated, postnatal bone mineralization compared to expected intrauterine bone mineralization and the pathogenesis of osteopenia investigated. Healthy babies (103 term, 76 preterm) were examined clinically, biochemically and radiologically the day after birth and at a time corresponding to expected full term gestation. Appendicular bone density was quantitated by magnification radiogrammetry, using the humeral cortical index (CI). The CI of preterm and term babies was similar the day after birth. In preterm babies elevated serum alkaline phosphatase and high urinary hydroxyproline indicated increased bone turnover. The CI of preterm babies at expected full term gestation was lower (p = 0.0001) than that of term babies at birth, implying that postnatal bone mineralization lagged behind expected intrauterine bone mineralization. Radiologic data suggested increased endosteal resorption rather than decreased bone formation. At expected full term gestation the preterm babies had higher serum alkaline phosphatase and urinary calcium, phosphate, c-AMP and hydroxyproline (p = 0.0001) than term babies at birth, and 15% had periosteal reactions. The biochemical as well as the radiologic data therefore indicated high turnover osteopenia in preterm babies. We conclude that postnatal bone mineralization in preterm babies lagged significantly behind expected intrauterine bone mineralization and that the osteopenia observed in preterm babies is caused by increased bone resorption and not by decreased bone formation. The cause(s) of this high turnover osteopenia, however, remains to be ascertained.

Low bone density is an etiologic factor for stress fractures in athletes.

OBJECTIVE: To determine whether low bone density and other risk factors for osteoporosis are associated with stress fractures in athletes. DESIGN: Case-control study. SETTING: Institutional sports injury clinic with primary and secondary care. PARTICIPANTS: Twenty-five athletes (nineteen women) with scintigraphically confirmed stress fractures matched for sex, age, weight, height, and exercise history with 25 control athletes with no history of bone injury. MEASUREMENTS AND MAIN RESULTS: Bone mineral density measured by dual-energy x-ray absorptiometry was significantly lower in athletes with fractures than in control athletes: In the spine, bone mineral density was 1.01 +/- 0.14 g/cm2 in athletes with fractures and 1.11 +/- 0.13 g/cm2 in control athletes (P = 0.02). In the femoral neck, it was 0.84 +/- 0.09 g/cm2 in athletes with fractures and 0.90 +/- 0.11 g/cm2 in control athletes (P = 0.005). It was also significantly lower in the Ward triangle (P = 0.01) and the greater trochanter (P = 0.01). Eight athletes with fractures and no control athletes had less than 90% of predicted age-related spine density (P = 0.01), and three athletes with fractures had bone mineral densities that were 2 SDs or more below this predicted level. More athletes with fractures than control athletes had current menstrual irregularity (amenorrhea or oligomenorrhea) (P less than 0.005). Fewer athletes with fractures were using oral contraceptives (P less than 0.05). Seven-day diet records indicated similar energy and nutrient intakes, except athletes with fractures had lower calcium intakes (697 +/- 242 mg/d compared with 832 +/- 309 mg/d; P = 0.02). Dairy product intake was lower in athletes with fractures since leaving high school (P less than 0.05). The incidence of a family history of osteoporosis was similar in both groups. CONCLUSIONS: In athletes with similar training habits, those with stress fractures are more likely to have lower bone density, lower dietary calcium intake, current menstrual irregularity, and lower oral contraceptive use.

Circulating acute phase reactive proteins as indicators of infection in poorly controlled diabetes mellitus.

Serum levels of six acute phase proteins (APP)--C-reactive protein (CRP), serum amyloid A (SAA), alpha 1-antitrypsin, haptoglobin and complement fractions C3 and C4--were serially studied in 24 patients with poorly controlled diabetes mellitus, ten of whom had unequivocal evidence of an underlying infection. In diabetic patients without infection, no change in APP levels was noted suggesting that hyperglycaemia per se does not quantitatively influence the acute phase response. No correlation between the presence of infection, and fever, leukocytosis, a raised erythrocyte sedimentation rate, or serum levels of alpha 1-antitrypsin, haptoglobin or complement was apparent in these patients. However, serum CRP and SAA were initially increased 10-100 times above normal in diabetic patients with an underlying infection (P less than 0.01); during the following week circulating levels of CRP and SAA decreased steadily in response to the infection being brought under control. We conclude that serial measurement of CRP and/or SAA is a sensitive, albeit non-specific, parameter to detect and monitor the activity of infection in patients with diabetes.

A previously undescribed ectodermal dysplasia of the tricho-odonto-onychial subgroup in a family.

We encountered two family members with a previously undescribed pure ectodermal dysplasia. The propositus exhibited hypotrichosis, hypodontia, focal linear dermal hypoplasia on the tip of her nose, irregular hyperpigmentation on her back, bilateral amastia and athelia, and mild nerve hearing loss. Her mother displayed similar characteristics, except for present, although hypoplastic, areolae and nipples. Both mother and daughter appeared to be clinically euhidrotic. Despite a comprehensive endocrine workup, the only abnormality detected was a suboptimal cortisol response to hypoglycemia in the propositus. Five other family members seemed to be affected. The pattern of inheritance appeared to be autosomal-dominant, with variable penetrance and expressivity.