Bone Mineral Accretion Research Articles

Skeletal requirements for optimal growth hormone replacement in the transitional years.

In addition to its well-established effects on linear growth in childhood and adolescence, growth hormone (GH) has both direct and indirect actions on bone remodelling and homeostasis. In this review, the discussion begins with the influence of childhood-onset growth hormone deficiency (CO-GHD) on bone mineral accretion. The limitations of methods of assessing bone mineral density (BMD) are highlighted and specific influential factors, which affect peak bone mass achievement and therefore skeletal health in later life, are evaluated.

Growth hormone replacement therapy (GHRT) in children and adolescents: Skeletal impact

In addition to its well-established effects on linear growth in childhood and adolescence, growth hormone has both direct and indirect actions on bone remodelling and homeostasis. In this review the limitations of methods of assessment of bone mineral density are highlighted. The influence of growth hormone deficiency of childhood-onset, on bone mineral accretion and, the specific skeletal implications of GHD in long-term survivors of childhood cancers, are discussed. Specific influential factors, which affect peak bone mass achievement and therefore skeletal health in later life, are evaluated.

Role of estrogen and androgen in pubertal skeletal physiology.

Since both estrogen and androgen are present in each sex, it has been difficult to discern the exact role that each sex steroid plays in skeletal physiology. However, studying clinical syndromes in which there is either only estrogen or androgen action has allowed us to gain insight into the unique role that each sex steroid plays in the growing skeleton. In complete androgen insensitivity syndrome (AIS) the only functional sex steroid receptor is that for estrogen. Effected XY females have a pubertal growth spurt that is typical of normal females, both in magnitude and timing. Individuals with AIS have a mild reduction in bone density but it is difficult to distinguish whether this is the result of androgen resistance or estrogen deficiency. These observations suggest that estrogen action only is sufficient to induce a normal pubertal growth spurt, epiphyseal maturation, and near normal bone mineral accretion in women. Until recently, the skeletal effects of estrogen were not thought to be of importance in the male. Conventional wisdom dictated that, in the male, testosterone mediated these skeletal changes. The notion that estrogen is of little importance in the male has been challenged by the recent discovery of two human syndromes in which estrogen action is lacking. In males with either estrogen resistance (inability to respond to circulating estrogen) or aromatase deficiency (inability to synthesize estradiol), as a result of the lack of estrogen action, a pubertal growth spurt does not appear to occur. Furthermore, complete epiphyseal maturation does not take place allowing for continued growth in adulthood and resultant tall stature. Finally normal bone mineral accretion does not take place resulting in severe osteoporosis. These findings indicate that estrogen plays a critical role in skeletal physiology of males as well as females.

Bone mineral density in children, adolescents and adults with glycogen storage disease type Ia: a cross-sectional and longitudinal study.

The occurrence of (symptoms related to) osteopenia is a known complication in glycogen storage disease type Ia (GSD Ia) patients. However, only limited information is available about bone mineral density (BMD). Using dual energy x-ray absorptiometry, we studied both cross-sectional and longitudinal lumbar spine areal BMD (BMD(areal) in g/cm2), areal BMD corrected for delayed bone maturation (BMD(bone age) in g/cm2), and volumetric BMD (BMD(vol) in g/cm3). Prepubertal GSD Ia patients (n = 8) had normal BMD (median z-scores BMD(areal) -0.6, BMD(bone age) -0.5 and BMD(vol) -0.5), whereas adolescent patients (n = 12) and adult patients (n = 9) had significantly reduced BMD (BMD(areal) -2.3, BMD(bone age) -1.6, BMD(vol) -2.0, and BMD(areal) -1.9, BMD(vol) -1.5, respectively). Our longitudinal study, showing a stable BMD(areal) but a trend to a decrease in BMD(vol) in prepubertal patients during follow-up, did not clarify whether the difference in BMD between prepubertal and adolescent/adult patients reflects a diminished accretion of BMD during childhood or reflects historical differences in treatment. In adolescent and adult GSD Ia patients, BMD(areal) and BMD(vol) were reduced but stable during follow-up. Especially patients with delayed bone maturation were at risk for reduced BMD. No correlation between parameters of metabolic control and BMD could be detected. Daily calcium intake was within recommended allowances ranges. Abnormal biochemical results included hypomagnesaemia (29%), hypercalciuria (34%) and reduced tubular resorption of phosphate (21%). Although the underlying pathophysiology of reduced BMD in GSD Ia remains unsolved, metabolic control should be optimized to correct as much as possible metabolic and endocrine abnormalities that may influence both bone matrix formation and bone mineral accretion.

Bones benefit from better biochemical control in type 1 glycogen storage disease

Bones benefit from better biochemical control in type 1 glycogen storage disease

Growth following malignancy.

Disturbed growth in the child surviving cancer is multifactorial. This chapter examines the evidence for, and the difficulties in determining, individual drug treatment or disease effects at multiple endocrine levels influencing growth and against a changing baseline of adjuvant cancer therapies with potentially additive toxicity. The evolutionary pattern and potential aetiology of the neuro-endocrine deficit and growth-plate disturbance, the (unrandomized) effects of hormone replacement therapy and areas which require further study are also addressed. The reasons why growth hormone (GH) secretion is so exquisitely sensitive to disturbance, even though deficiencies soon after lesser cranial insults can be difficult to detect, are explored with evidence cited from the few existing prospective and interventional studies. The extent and nature of the hypothalamo-pituitary disturbance needs further prospective interventional study and disease-site- and treatment-specific comparisons. Practical treatment and surveillance strategies to optimize growth potential, age-appropriate development, peak bone mineral accretion, hair re-growth and future health and well-being are also suggested. Health-related outcomes resulting from today's newer therapies and enhanced surveillance need documenting in future (inter)national cancer trials, where randomized studies of hormonal intervention may also become possible.

Reduced bone mass in children with idiopathic hypercalciuria and in their asymptomatic mothers.

Patients with nephrolithiasis and idiopathic hypercalciuria (IH) may exhibit reduced bone mineral density (BMD). Most studies measuring BMD in IH patients employing dual-energy X-ray absorptiometry (DEXA) have been performed in adults, and no study has been conducted in North-American children. Optimal bone mineral accretion during childhood and adolescence is critical to the attainment of a healthy adult skeleton. Bone mineral accretion and eventual adult peak bone mass are largely dependent on genetic factors. Hypercalciuria is also frequently linked to genetic determinants. Therefore, we carried out a cross-sectional evaluation of bone mineral metabolism in children with IH, and in their asymptomatic premenopausal mothers. Quantitative BMD using DEXA was performed in 21 children with IH and in their asymptomatic mothers. Bone resorption was assessed by measuring the urinary concentrations of pyridinoline and deoxypiridinoline. Simultaneous calcium-modulating hormonal determinations, including serum intact immunoreactive parathyroid hormone and 1,25(OH)(2)D(3), were performed. The expression of interleukin-1alpha (IL-1alpha) by peripheral blood mononuclear cells (PBMCs) was determined by polymerase chain reaction. Reduced BMD values were observed in eight children (38%) and in seven mothers (33%). The children of osteopenic mothers exhibited significantly reduced BMD Z-score values of lumbar spine (P<0.05) when compared with children of mothers with normal BMD. Bone resorption markers were normal in most children with IH. Hypercalciuria was detected in five out of 20 (25%) asymptomatic mothers and it correlated (r=-0.81) to femoral BMD in mothers with osteopenia. The expression of IL-1alpha mRNA by PBMCs from IH children did not differ from controls. Reduced BMD was detected in a large proportion of children with IH. Hypercalciuria and reduced BMD were uncovered in a substantial number of their otherwise healthy asymptomatic mothers. The diminished BMD in adults with IH may start early in life, could be influenced by genetic factors, and may represent a risk factor for osteoporosis later in life.

Inflammatory bowel disease in children and adolescents: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Inflammatory bowel disease in children and adolescents: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Recovery from osteoporosis through skeletal growth: early bone mass acquisition has little effect on adult bone density.

It is often assumed that bone mineral accretion should be optimized throughout childhood to maximize peak bone mass. In contrast, we hypothesized that bone mineral acquisition early in life would have little or no effect on adult bone mass because many areas of the juvenile skeleton are replaced in toto through skeletal growth. To test this hypothesis, we induced osteoporosis by administering dexamethasone to 5-week-old rabbits for 5 weeks and then allowed them to recover for 16 weeks. Tibial bone mineral density (ash weight/volume) was decreased in the dexamethasone-treated animals at the end of treatment but recovered completely. Bone structure in the femur was assessed by histomorphometry. Trabecular and cortical bone in the distal metaphysis was made osteoporotic by dexamethasone, but was then replaced through endochondral bone formation and recovered. Periosteal bone formation rate in the diaphysis was decreased during dexamethasone treatment but afterwards rebounded above controls and normalized cortical width. Our data suggest that bone mineral acquisition early in life has little effect on adult bone density because the juvenile bone is largely replaced through growth. If this concept generalizes, then interventions to maximize peak bone mass should be directed at adolescents rather than young children.

Bone Maturation and Bone Mineralization in Precocious Puberty: Relation to Estrogen Receptor Gene Polymorphisms.

Estrogen plays an important role in bone maturation and bone mineralization. To elucidate the physiological roles of estrogen in the regulation of bone growth, we investigated the relationship between bone mineral status and the estrogen receptor (ER) gene polymorphism in subjects with precocious puberty, where excess estrogen is exposed to the bone. Thirty-six patients with central precocious puberty or early puberty were enrolled in the study. The relationships between PvuII and XbaI restriction fragment length polymorphisms of the ER gene and the lumbar spine bone mineral density (BMD), BMD SD score adjusted for either chronological age or bone age, were evaluated. The mean BMD value for bone age (-0.52 ± 0.83 SD) was significantly lower than the BMD value for chronological age (0.30 ± 0.96 SD) (p<0.01), indicating that bone maturation (advancement of bone age) was not associated with bone age-matched mineralization (increase in BMD). Furthermore, the PP genotype for the PvuII polymorphism appeared to be associated with an increased BMD (p<0.05), suggesting that the ER gene genotype may be related to bone mineral accretion during estrogen exposure. ER gene polymorphisms might thus account for the varying degrees of increase in BMD after estrogen exposure, leading to the dissociation of bone maturation and bone mineralization.

Impact of lung inflammation on bone metabolism in adolescents with cystic fibrosis

Deficits in bone mineral density resulting in premature osteopenia and osteoporosis have been documented in cystic fibrosis patients for over 20 years. A high incidence of fractures and kyphosis in the continually increasing adult patient population and in post-lung transplant patients has highlighted the problems associated with poor bone health.The aetiology of osteoporosis in CF is multifactorial but centres on an uncoupling in the normal balance between bone formation and resorption. Delayed puberty, malabsorption and reduced weight-bearing exercise can result in inadequate bone mineral accretion in childhood and adolescence. Corticosteroid use and pro-inflammatory cytokines associated with infective respiratory exacerbations can accelerate bone loss. Dual energy X-ray absorptiometry is the most commonly available technique to measure bone mineral density. All patients should be scanned at least every 2 years from adolescence. The treatment of established disease with bisphosphonates shows encouraging early results.

The influence of calcium intake and physical activity on bone mineral content and bone size in healthy children and adolescents.

Studies of determinants of bone mineralization during growth are relevant to the attempt to increase peak bone mass. The aim of this study was to examine how calcium intake and physical activity influence bone size (bone area, BA), accretion in BA, whole body bone mineral content (BMC) and accretion in BMC. BA and BMC were examined by dual-energy X-ray absorptiometry (Hologic 1000/W) in healthy girls (n = 192) and boys (n = 140) aged 5-19 years at baseline and 1 year later. Calcium intake was assessed three times by a food frequency questionnaire and physical activity three times by a 24 h recall questionnaire. The influence of calcium intake and physical activity was examined by multiple regression. BA was size-adjusted by including height and weight in all analyses, and BMC was size-adjusted by including BA, height and weight in all analyses. Size-adjusted average BA was associated neither with average calcium intake nor with average physical activity. Size-adjusted accretion in BA was borderline associated with the average calcium intake in boys only (p = 0.07). Size-adjusted average BMC was positively associated with average calcium intake (p) = 0.03 girls; p = 0.07 boys) and borderline associated with average physical activity level in boys (p = 0.07) but not girls (p = 0.7). Size-adjusted accretion in BMC was significantly associated neither with average calcium intake nor with average physical activity level, but was associated with change in calcium intake over the 1 year observation period in boys (p = 0.03) but not girls (p = 0.9). In conclusion, we found that size-adjusted BMC in school-aged children was positively associated with average calcium intake. Size-adjusted accretion in BMC was positively associated with change in dietary calcium intake in boys only. To what degree this is caused by a reduction in remodeling space is unknown.

MINI-SYMPOSIUM

This symposium addresses the enormous economic and emotional burden placed on health care systems and individuals by osteoporosis. Although there has been a dramatic increase in evidence that exercise promotes bone health, the need for differing exercise prescriptions at different stages of the life-span is often overlooked. In this session we will introduce lifestyle interventions, that have been utilized across different age groups to prevent osteoporotic fracture. The specific purpose of this symposium is to outline exercise intervention programs that: increase bone mass and strength in growing children. improve the bone health of postmenopausal women. reduce the major risk factors for falls in women with osteopenia, osteoporosis or previous fracture. It has been suggested that mechanical loading forces are not as effective in inducing bone mineral accretion in aged bones as in young bones Dr. McKay will discuss the positive role of exercise in promoting childhood bone mineral accrual and describe the large school based exercise intervention RCT that proved effective in increasing bone mass in children. In postmenopausal women there is evidence that the same mechanical stresses that are osteogenic in young women fail to induce increases in bone mineral density. This suggests that the capacity of bone to adapt to mechanical stress may deteriorate with aging. Dr. Kohrt will discuss the possibility that age-related or menopause-triggered changes in such factors as hormones or growth factors may underpin the osteogenic response to mechanical stress with aging. The final speaker will emphasize the need for exercise prescription in the frail elderly and those with established osteoporosis. The focus will be on the role of exercise in reducing fall risk by improving muscle strength and balance. Other fall risk factors must also be ameliorated. In summary, this symposium combines scientific updates of recent years with practical solutions for ACSM members interested in physical activity and bone health across the lifespan.

Follow-Up Examination at the Age of 15 Months of Extremely Preterm Infants after Postnatal Estradiol and Progesterone Replacement

A randomized controlled pilot study was performed with a sample of extremely preterm infants to evaluate the impact of postnatal estradiol and progesterone replacement on postnatal bone mineral accretion. Twenty-five of 30 infants in the pilot study survived, and of these, 24 infants were available for the follow-up examination at a median chronological age of 18.1 months (minimum-maximum, 17.0–20.6) corresponding to a corrected age of 14.8 months (minimum-maximum, 12.9–17.4). Somatic growth data and bone mineralization showed no differences between the hormone-treated and control group infants. The deviation of the skeletal age from the corrected age was 0.0 months (minimum-maximum, −7.7 to 7.4) for hormone-treated infants compared with −1.7 months (minimum-maximum, −7.5 to 5.9) for the control group. The Bayley scales mental and psychomotor developmental indexes were 89 (minimum-maximum, 71–107) and 101 (minimum-maximum, 49–121) for the hormone-treated infants and 93 (minimum-maximum, 49–111) and 71 (minimum-maximum, 49–121) for the control group infants, respectively (mental developmental index, P = 1.0; psychomotor developmental index, P = 0.14). The normal psychomotor development in the hormone-treated infants compared with the below average development in the control group infants is encouraging and indicates the potentially important integrative role of sex steroids for the developing brain. Larger studies on the effects of the postnatal replacement of estradiol and progesterone in extremely preterm infants are warranted.

Management of the extremely preterm infant: is the replacement of estradiol and progesterone beneficial?

This review presents data to suggest that postnatal estradiol and progesterone replacement therapy may be beneficial in preterm infants. During pregnancy, maternal plasma levels of estradiol and progesterone increase up to 100-fold compared to the nonpregnant status. The fetus is also exposed to these increasing hormone levels. After delivery, estradiol and progesterone levels drop by a factor of 100 within 1 day. Whereas this is a physiological condition for an infant born at term, preterm delivery means withdrawal from the placental supply of these hormones at an earlier developmental stage. Seventy years ago, the idea was raised that preterm infants may benefit from the replacement of estrogens. Studies in which estrogen was injected subcutaneously showed only a slightly better bodyweight gain compared to placebo-treated controls and therefore routine use was not established. The effective treatment of postmenopausal osteoporosis with hormone replacement therapy led to a pilot study of estradiol and progesterone therapy to prevent osteopenia of prematurity. The highest median bone mineral accretion rate was found in the replacement group when the supplementation with calcium and phosphorus was also sufficient. None of the previous studies dealing with estrogen replacement controlled for achieved plasma levels of estradiol in the infants. In our controlled randomised pilot study with 30 preterm infants (15 in each group), we aimed to maintain intra-uterine plasma levels of estradiol and progesterone. Preterm infants with replacement of estradiol and progesterone for 6 weeks postnatally showed trends to higher bone mineral accumulation. In addition, a trend towards a lower incidence of chronic lung disease was found. Neurodevelopmental follow-up showed normal psychomotor development in infants given estradiol and progesterone, whereas the untreated infants (controls) showed a trend towards delayed development. Recent research emphasises that estradiol and progesterone may be important for brain development. Thus, while there is data indicating that postnatal estradiol and progesterone replacement therapy may be beneficial in preterm infants, experience with this new therapy is limited and extensive research is needed to address the potential benefits and to rule out adverse effects.

Estrogen agonist (zeranol) treatment in a castrated male lamb model: effects on growth and bone mineral accretion.

The mechanism of estrogen's action on bone mineralization in children has received little attention. Our objective was to determine the effect of time (developmentally) and duration of exposure to an estrogen agonist (zeranol) on bone growth and mineralization using a castrated male lamb model. At birth, 40 male lambs were castrated and within 14 days of birth (day = 0) they were assigned (n = 10 per group) to age-matched control lambs (C-AGE) or to receive a 12.5-mg zeranol implant as follows: E-0, implanted on days 0, 45, 90, and 135; E-90, implanted on days 90 and 135; and E-0, 90, implanted on days 0, 90, and 135. Lambs were studied for 163 days. Serum was collected on days 28, 73, 118, 135, and 163 and analyzed for minerals (Ca, P, and Mg), markers of bone remodeling (bone alkaline phosphatase [ALP] and tartrate resistant acid phosphatase [TRAP]), 1,25-dihydroxyvitamin D [1,25(OH)2D], growth hormone (GH), and insulin-like growth factor I (IGF-I). Whole-body bone mineral content (BMC), bone mineral density (BMD), fat mass, and lean mass were determined by dual energy X-ray absorptiometry (DEXA) on days 28, 73, 118, and 163. There was a linear increase in growth at all time points. Whole-body BMC, weight, and lean mass of C-AGE and E-90 lambs were less than E-0, and E-0, 90 lambs at all time points. Whole-body BMD of C-AGE and E-90 lambs was less than E-0 and E-0, 90 lambs at 28 days and 73 days; however, after implantation at day 90 whole-body BMD of E-90 lambs was similar to E-0 and E-0, 90 lambs at day 118 and day 163 and all three were greater than C-AGE lambs. There was no effect of treatment on calcium absorption, serum minerals, hormones, or markers of bone remodeling. We conclude from these data that treatment of growing castrated lambs with an estrogen agonist from birth augments growth, whereas delaying estrogen agonist treatment does not facilitate growth but appears to augment bone mineral accretion. We suggest these observations may have clinical relevance, and deserve consideration when treating children with delays in growth and bone mineral accretion.

Lactation Delays Postpartum Bone Mineral Accretion and Temporarily Alters Its Regional Distribution in Women

The objective of this work was to compare long-term changes in bone mineral in lactating (L) and nonlactating (NL) women for 2 y postpartum. The 40 L women (mean duration of breastfeeding 345 +/- 177 d) and 36 NL women were enrolled during late pregnancy. Subjects were healthy and nonsmoking with a mean age of 28.8 +/- 4.1 y. Bone mineral content (BMC) was measured at 0.5, 3, 6, 12, 18 and 24 mo by dual-energy X-ray absorptiometry set for total body scan with regional analysis. BMC adjusted for bone area, weight and height (adj-BMC) decreased in L women at the lumbar spine (-3.1%, P < 0. 001) and pelvis (-0.9%, P = 0.03) by 3 mo, and at the total body (-0. 9%, P = 0.05) by 6 mo. Losses were recovered following onset of menses. Adj-BMC at the lumbar spine, pelvis, thoracic spine and total body increased over baseline by 24 mo in L women. In NL women, adj-BMC increased over baseline within 3 mo and continued to increase thereafter. Net total-body gains were greater in the 27 NL women who completed the final measurement than in their 26 L counterparts (+2.3% vs. +0.6%, P = 0.001). Net regional gains differed at the head, legs, and ribs, but not at the lumber spine, pelvis or thoracic spine. Duration of breastfeeding, parity, onset of menses and maternal age affected bone changes in L women. These results indicate that lactation delays bone mineral accretion and temporarily alters its regional distribution in postpartum women.

Effect of calcium supplementation on bone mineral accretion in Gambian children accustomed to a low-calcium diet

Rural Gambian children have poor growth, delayed puberty, a low bone mineral content, and a low calcium intake. We investigated the effect of a calcium supplement on bone mineral accretion in rural Gambian children. A randomized, double-blind, placebo-controlled study was conducted in 160 children (80 boys, 80 girls) aged 8.3-11.9 y. Bone mineral content (BMC), bone mineral density (BMD), and BMC adjusted for bone width, body weight, and height (size-adjusted BMC) were measured at the midshaft and distal radius. Each child received either 1000 mg Ca/d (as calcium carbonate) or a placebo 5 d/wk for 12 mo. Supplementation increased calcium intake from 342 to 1056 mg/d (8.6 to 26.4 mmol/d). Calcium supplementation resulted in a higher BMC, BMD, and size-adjusted BMC (&xmacr; difference +/- SE): midshaft radius-BMC (3.0 +/- 1.4%; P = 0.034), BMD (4.5 +/- 0.9%; P </= 0.0001), and size-adjusted BMC (4.6 +/- 0.9%; P </= 0.0001); distal radius-BMC (8. 4 +/- 3.2%; P = 0.009), BMD (7.0 +/- 2.7%; P = 0.011), and size-adjusted BMC (5.5 +/- 2.7%; P = 0.042). Supplementation had no significant effect on height, weight, or bone width at the midshaft radius or distal radius. At the end of the study, the calcium group had a significantly lower mean plasma osteocalcin concentration than the placebo group after adjustment for baseline concentration, sex, and pubertal status (-21.9 +/- 6.5%; P = 0.001). Increased calcium intake resulted in increased bone mineral status, possibly in association with a decreased bone remodeling space. Further studies are needed to determine whether an increased calcium intake has long-term benefits in Gambian children.

Effects of Postnatal Estradiol and Progesterone Replacement in Extremely Preterm Infants

The fetus is supplied from the placenta with estradiol (E2) and progesterone (P) in increasing amounts during gestation. After delivery of a premature infant, placental supply is disrupted, resulting in a rapid decrease in E2 and P. Replacement of these placental hormones may restore intrauterine conditions and may be beneficial for bone mineral accretion, clinical course, and outcome. Thirty female infants with a median gestational age of 26.6 weeks (between 24.1–28.7) and a birth weight of 675 g (370–990) were randomized to receive E2 and P replacement, aiming to maintain plasma levels equaling the intrauterine levels, or no replacement. The E2 and P replacement was started iv and was followed by transepidermal administration for a total duration of 6 weeks. Repeated measurements included plasma levels of E2, P, FSH, and LH; uterine volume; calcium and phosphorus in spot urine specimens; and bone mineral accretion by single photon absorption densitometry. Further, the incidence of chronic lung disease and various clinical outcome data were recorded. The plasma levels of E2 and P were within the intrauterine range with median replacements of 2.30 mg/kg·day E2 (1.13–6.23) and 21.20 mg/kg·day P (11.23–27.36), iv. Three- and 6-fold higher doses of E2 and P were needed via the transepidermal route. The uterine volumes increased, and FSH and LH as indicators for biological effectiveness were significantly lowered with replacement. The bone mineral accretion rates tended to be higher, and the incidence of chronic lung disease tended to be lower (0% vs. 29%; P = 0.097). E2 and P replacement via iv and transepidermal routes is capable of maintaining plasma levels as high as those in utero with biological effectiveness. Trends toward improved postnatal bone mineral accretion and less chronic lung disease were found with the hormone replacement. Further and more extensive studies are warranted to address the role of this new approach in the care of extremely premature infants.

Bone and collagen markers in preterm infants: relationship with growth and bone mineral content over the first 10 weeks of life.

In a longitudinal study of 25 preterm infants, we have examined the relationship of bone-specific alkaline phosphatase (ALP), C-terminal propeptide of type I collagen (PICP), N-terminal propeptide of type III procollagen (P3NP), C-terminal telopeptide of type I collagen, urinary pyridinoline (Pyd) and deoxypyridinoline (Dpd), with rates of gain in weight, length, and lower leg length and with bone mineral content (BMC), all measured at weekly intervals over the first 10 wk of life. Concentrations of all collagen markers were 10-fold higher than in older children. Each marker showed a distinctive pattern of postnatal change, with early increases in PICP and P3NP and decreases in ICTP reflecting postnatal growth. Once markers had reached a plateau during weeks 4-10, P3NP was positively correlated, whereas Pyd and Dpd were negatively correlated with rate of weight gain (r = +0.44, -0.46, and -0.40, respectively, p < 0.05). P3NP was also positively correlated with overall linear growth (r = +0.44, p < 0.05). PICP was strongly correlated with mean BMC (r = +0.63,p < 0.01) and with total BMC attained by the end of the study period (r = +0.81, p < 0.001). Bone ALP was positively correlated with the rate of bone mineral accretion (r = +0.55, p = 0.01). We conclude that the marker of soft-tissue collagen formation, P3NP, is a good marker for overall ponderal and linear growth in preterm infants, whereas the markers of collagen breakdown, Pyd and Dpd, have inverse relationships with weight gain. The osteoblast markers, PICP and bone ALP, seem to be good surrogate markers for bone mineralization in preterm infants. Markers may provide information on whole-body turnover of bone and collagen that is complementary to traditional physical measures of growth and bone mineralization.