Urinary galactosyl-hydroxylysine in postmenopausal osteoporotic women: A potential marker of bone fragility.

Alterations of the collagen matrix, e.g., increased hydroxylation and glycosylation of lysyl residues in collagen I, were found in human osteoporotic bone, and it was suggested that they could alter the mechanical properties of skeleton. To test this hypothesis, we evaluated the content of galactosyl-hydroxylysine (GHYL) in bone collagen, as assessed by its urinary excretion, and related it to the occurrence of fracture. Two hundred and fifteen unselected postmenopausal women with osteoporosis were divided in two subgroups (comparable for age, age of menopause, bone mineral density, and biochemical parameters of bone turnover) on the basis of the history of fragility fracture; 115 patients had suffered no fracture and 100 patients had suffered one or more fractures 3 or more years before. Four urinary markers of bone turnover (hydroxyproline, cross-linked N-telopeptide, free deoxypyridoline, and GHYL) were evaluated in all patients. There was no difference between the two groups with regard to all the parameters studied except for GHYL, which was significantly higher in the group with a history of fracture (1.35 +/- 0.82 mmol/mol of creatinine [Cr] versus 1.03 +/- <0.48 mmol/mol Cr, p < 0.001); this marker did not correlate with other markers of bone remodeling in the fracture group, indicating a possible defect in bone collagen. In conclusion, provided that increased levels of urinary GHYL do reflect overglycosylation of hydroxylysine in bone collagen, the GHYL may be considered a marker of bone collagen quality. Our results, showing higher urinary GHYL in osteoporosis patients with fracture, seem to confirm this suggestion.

Prevention of bone demineralization by calcium supplementation in precocious puberty during gonadotropin-releasing hormone agonist treatment.

We have previously demonstrated a negative impact on peak bone mass in girls with precocious puberty treated with GnRH agonist (GnRHa). Several studies have shown that a high calcium intake positively influences bone mass in prepubertal girls and leads to a higher peak bone mass. The aim of this study was to evaluate the effect of calcium supplementation in girls with precocious puberty during GnRHa treatment. Forty girls affected by true central precocious puberty and treated with the GnRHa triptorelin were studied for 2 yr. After diagnosis, the patients were randomly assigned to three groups: group A, treated only with GnRHa; group B, treated for 12 months solely with GnRHa and then supplemented with calcium gluconolactate/carbonate (1 g calcium/day in two doses) for 12 months; and group C, treated from the beginning with combined GnRHa and calcium. Bone mineral density (BMD) at the lumbar spine was measured by dual energy x-ray absorptiometry at the beginning of the study and after 12 and 24 months and was expressed as the calculated true volumetric density (BMDv) in milligrams per cm3. Group A showed a decrease in absolute BMDv levels, in SD score for chronological age (CA), and even more in SD score for bone age (BA). Group B showed the same behavior during the first year, but this trend was reversed in the second year, when calcium supplementation was added to GnRHa treatment. Group C showed an increase in absolute BMDv levels and in SD score for CA and BA. BMDv variations (expressed as absolute values, SD score for CA, and SD score for BA) became statistically significant at 24 months between groups C and A (P = 0.036, P = 0.032, and P = 0.025, respectively). The behavior of the lumbar spine BMDv in the three groups is consistent with a positive effect of calcium supplementation during GnRHa treatment. In calcium-supplemented patients, the normal process of bone mass accretion at puberty is preserved despite GnRHa treatment. Therefore, the reduction in BMD during GnRHa treatment in girls with precocious puberty is at least completely reversible and preventable if calcium supplementation is associated from the beginning.

Longitudinal evaluation of bone mass in asthmatic children treated with inhaled beclomethasone dipropionate or cromolyn sodium.

Inhaled corticosteroids are recommended as first-line therapy in patients with moderate to severe asthma. The use of these agents in the milder form of asthma is controversial because of their potential adverse effects, especially in growing children. We investigated 49 asthmatic children (38 treated with beclomethasone dipropionate (BDP) at a daily dose of 276+/-125 microg/day and 11 treated with cromolyn sodium (CS) at a daily dose of 30+/-10 mg/day) for 7.4 months, with bone-mass measurements at baseline and after the treatment period. Evaluation of changes in cortical and trabecular bone mass (bone mineral density [BMD]; m/cm2) was performed by absorptiometry at the proximal forearm and at the lumbar spine, respectively. Furthermore, to correct for bone size changes due to growth, we calculated volumetric BMD (VOL-BMD; mg/cm3). At the end of the treatment period, the children who had received regular inhaled BDP had grown as well as children treated with CS, from 120+/-1.4 to 123+/-1.3 cm and from 118+/-3.2 to 120.3+/-2.8 cm, respectively. No children showed deviation from their percentile level of growth. Trabecular and cortical BMD increased after 7 months of follow-up in both groups to the same extent. When BMD was adjusted for body size (VOL-BMD; mg/cm3), bone mass was found not to have changed after BDP or CS treatment course within and between the two groups.

Effect on cortical and trabecular bone mass of different anti-inflammatory treatments in preadolescent children with chronic asthma.

Bone metabolism and density have been shown to be abnormal in adult asthmatic patients treated with inhaled corticosteroids. Because the largest increases in bone growth and mineral deposition occur during childhood and adolescence, we performed a cross-sectional evaluation of cortical and trabecular bone mass by dual-photon absorptiometry at the proximal one third of the radius (cortical bone) and by dual-energy X-ray absorptiometry at the L2-L4 lumbar spine (trabecular bone) in 64 prepubertal asthmatic children receiving beclomethasone dipropionate (BDP) or cromolyn sodium (CS). Dual-energy X-ray absorptiometry was performed by anteroposterior scan and also by lateral vertebral scan in order to exclude the posterior elements of the vertebrae, which are composed mainly of cortical bone and which are less sensitive to the negative effect of steroids. Furthermore, we calculated "volumetric" bone density, dividing lateral mineral content by the vertebral volume. Bone mineral areal density and volume bone density did not differ in children receiving BDP for 6.7 +/- 1.3 mo at a mean dose of 319.3 +/- 130 micrograms/d compared with those in children treated with CS. Furthermore, anteroposterior bone density in our study population was in agreement with published normative data and with that of normal age-related healthy nonasthmatic children living in the same area and with the same dietary intake of calcium. No normal values are available for lateral and calculated-volume bone density. In conclusion, treatment with BDP does not appear to have an adverse effect on bone mass in prepubertal children with mild moderate asthma. Longitudinal studies should be performed in order to evaluate the effect of early introduction of inhaled corticosteroids in children with mild asthma.