Bone Growth Rate Research Articles

Prostaglandin E2 administration prevents bone loss induced by orchidectomy in rats

The objects of this study were to investigate whether prostaglandin E2 (PGE2) can prevent orchidectomy (ORX)-induced cancellous bone loss in growing male rats, and to determine the differential effects of PGE2 on sham-operated (sham) and ORX male rats. Fourteen-week-old Sprague-Dawley male rats were divided into groups of basal, vehicle-treated sham, PGE2-treated sham, vehicle-treated ORX, and PGE2-treated ORX rats for either 3 or 9 weeks. PGE2 was given at 6 mg/kg body weight daily by subcutaneous injection. Static and dynamic cancellous bone histomorphometry were performed on double-fluorescent labeled undecalcified proximal tibial metaphyseal sections. No effect was observed by ORX on body weight or longitudinal bone growth rate when compared with sham-operated controls. However, androgen deficiency caused significant increases in percent eroded perimeter, mineral apposition rate, and bone turnover (bone-volume-referent-bone formation rate), which resulted in a significant decrease in trabecular bone number, increase in trabecular separation, and a nonsignificant decrease in trabecular bone area by 3 weeks of ORX. After 9 weeks of ORX, trabecular bone area and number were significantly decreased, and trabecular separation, percent eroded perimeter, and the index of bone turnover (bone-volume-referent-bone formation rate) remained significantly increased while the index of bone formation (tissue-volume-referent-bone formation rate) was nonsignificantly decreased when compared with sham controls. When 6 mg PGE2/kg/day was given for 3 and 9 weeks, similar anabolic effects were observed in sham and ORX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of prostaglandin E 2 and risedronate administration on cancellous bone in older female rats

The effects of Prostaglandin E 2 (PGE 2) and Risedronate (Ris) both separately and in combination (PGE 2 + Ris) were studied on the intact aged female rat skeleton to determine whether the combination of PGE 2 with an antiresorptive agent is more effective anabolically than PGE 2 alone. Ninemonth-old Sprague-Dawley rats were injected subcutaneously either with vehicle, 6 mg PGE 2/kg per day, 1 or 5 μg Ris/kg twice a week, or 6 mg PGE 2/kg per day plus 1 or 5 μg Ris/kg twice a week (PGE 2 + 1 Ris or PGE 2 + 5 Ris) for 60 days. After the treatment, we determined the longitudinal bone growth rate, the qualitative appearance of the primary spongiosa (PS), and the static and dynamic bone histomorphometry of the secondary spongiosa (SS) of the proximal tibial metaphysis (PTM) by examining undecalcified longitudinal sections after double-fluorescent labeling. The relative effects of these treatments on longitudinal bone growth were ranked as follows: PGE 2 + 5 Ris > PGE 2 + 1 Ris = basal > PGE 2 > 1 μg Ris = 5 μg Ris = aging. The density of the PS was ranked as follows: PGE 2 + 5 Ris > PGE 2 + 1 Ris = PGE 2 = 5 μg Ris = 1 μg Ris > basal = aging. The increase in density of the PS was the result of stimulated longitudinal growth and the action of bisphos + phonate. Bone mass in the SS was ranked as follows: PGE 2 + 5 Ris = PGE 2 + 1 Ris = PGE 2 > 5 μg Ris = 1 μg Ris = aging = basal. However, PGE 2 alone and its cotreatment with Ris accumulated bone by different tissue mechanisms. PGE 2 alone created new bone by increasing activation frequency 8.3-fold and the formation to resorption ratio 1.3-fold from the controls. The combination of PGE 2 and Ris depressed activation frequency (−54% to −74%), and bone formation rate (tissue-based −31%, and bone-based −42%) and eroded surface (−79% to −81%), so as to increase the formation to resorption ratio (three- to four-fold) over PGE 2 alone. The increased ratio was due primarily to a greater decrease in eroded perimeter than in labeled perimeter. The major finding of this study is that the combination of PGE 2 and a bisphosphonate (Ris) is more anabolic than PGE 2 or Ris alone when endochondral ossification is active, but PGE 2 + Ris is no more anabolic than PGE 2 alone in old bone without endochondral ossification. However, the tissue mechanisms by which PGE 2 alone and PGE 2 + Ris treatments accumulated bone differed in that the latter allowed the same bone mass to accumulate with lower levels of cell recruitment and activity.

Stereological and serial section analysis of chondrocytic enlargement in the proximal tibial growth plate of the rat.

It has been suggested that within the growth plate, the final volume and shape of hypertrophic chondrocytes are important variables in determining the rate of longitudinal bone growth. To better understand the organization and regulation of chondrocytic hypertrophy as related to longitudinal bone growth, the beginning and end, and the location and magnitude of chondrocytic volume and shape changes during the hypertrophic process were defined in the proximal tibial growth plate of 35-day-old rats. In this study we used two different approaches, a stereological analysis of chondrocytes in unbiasedly defined, narrow growth plate strata, and a serial section reconstruction and measurement of individual cells. In both experiments chondrocytes were preserved using optimal chemical fixation. Proliferating chondrocytes were identified using bromodeoxyuridine labelling, and the rate of longitudinal bone growth was determined using oxytetracycline labelling. In both studies, immediately following cell division in the proliferative zone, chondrocytic volume gradually increased toward the mid-point of the growth plate. During this phase of about 30 hours, approximately 20% of the final cell volume was obtained. During the following 20 hours the remaining 80% was acquired. The estimated rate of cell volume increased changed from approximately 50 microns 3/hr during the first 30 hours to about 800 microns 3/hr during the last 20 hours. The increase in cell volume resulted in an increase in both the vertical and the horizontal chondrocytic diameters. Cell parameters did not change during the final five hours of the maturation process. In this study we demonstrated that chondrocytic enlargement starts immediately following cell division in the proliferative zone, and that chondrocytic enlargement consists of two morphologically distinguishable phases. The transition point between the first and the second phase of chondrocytic enlargement corresponded with the junction between the proliferative zone and the maturation zone.

Effects of a non-steroidal pure antioestrogen, ZM 189,154, on oestrogen target organs of the rat including bones.

ZM 189,154 ([1RS,2RS]-2-(4-hydroxyphenyl)-2-methyl- 1-[9-(4,4,5,5,5-penta-fluoropentyl)sulphinylnonyl]-1,2,3,4- tetrahydronaphth-6-ol) is a non-steroidal pure antioestrogen. It has a high relative affinity for the oestrogen receptor, completely blocks the trophic action of oestradiol (OE2) on the uterus in immature and ovariectomized (OVX) adult rats and, in the latter, also completely blocks the trophic action of OE2 on vagina, bone and growth rate. ZM 189,154 displays no intrinsic oestrogen-agonist activity on uterus, vagina, bone, LH secretion or growth rate in OVX rats. Differential sensitivity of OE2-regulated processes was more apparent in intact rats. Daily doses of 0.6 mg/kg per day of ZM 189,154 blocked ovulation; 2 mg/kg per day achieved maximal uterine atrophy but did not affect bone density or growth rate; 10 mg/kg per day produced a broader spectrum of effects (reduced bone density, increased basal LH, slightly increased growth rate), but the magnitude of these was smaller than after ovariectomy; the 10 mg/kg dose also produced multiple ovarian follicular cysts. The failure of ZM 189,154 to achieve complete ovariectomy-like effects in intact rats may be due to the action of ovarian factors other than OE2, or to the circulating OE2 levels resulting from the disturbance to ovarian function posing too strong a challenge to the antagonist.

Systemic administration of recombinant transforming growth factor beta 2 (rTGF-β2) stimulates parameters of cancellous bone formation in juvenile and adult rats

Transforming growth factor β is a multifunctional protein with known actions on bone and bone cells. The ability of TGF-β to stimulate osteogenic parameters in vitro and osteogenesis adjacent to injection sites in vivo is well established. The purpose of this study was to determine if systemic administration of recombinant TGF-β2 (rTGF-β2) could stimulate bone formation in rats of different ages. Juvenile (25-day-old) and adult (160-day-old) rats were treated daily for 5 days and 14 days, respectively, with rTGF-β2 given by subcutaneous injection. Bone formation was measured in cancellous bone of the lumbar vertebrae in juvenile rats and the femoral epiphysis in adult rats. Endochondral bone growth rates were measured in the distal femurs from both juvenile and adult rats using histomorphometric methods. Systemic administration of rTGF-β2 resulted in substantial increases in bone formation rates (both surface and volume referent) in both juvenile and adult rats. In the juvenile rats, rTGF-β2 increased the percent double labeled surface and the mineral appositional rate. In the adult rats, TGF-β2 treatment increased the double labeled surface and also endochondral (longitudinal) growth parameters without changing the number of osteoclasts or the number of osteoclast nuclei per cell. These results demonstrate that short-term systemic administration of rTGF-β2 substantially increases cancellous bone formation rate in rats.

Comparative quantitative histology of mammalian growth plates

Variation in the growth rate of long bones is a function of the number of dividing cells in the columns of the proliferation (flat) cell zone of the growth plate, the frequency with which they divide, and the size to which they grow prior to ossification. In a previous study we found that the wide variation in bone growth rates seen among species of birds was largely associated with variation in the numbers of cells in the flat cell zone. Here we have undertaken a similar study of the growth plates of mammals and have examined variation in the morphology and cell kinetics of the tibial growth plates of a variety of species. The bone growth rates tended to he lower than those observed in birds and were particularly low in the anthropoid primates. Although quite marked variation in flat cell numbers is apparent, the results suggest that variation in cell division rate may play a relatively greater role in variation in bone growth rate among mammals than it does in birds. and that the very low hone growth rates seen in the primates are due, in part, to lower rates of cell division than in other species.

Factors affecting urinary pyridinoline and deoxypyridinoline excretion in the growing lamb

Changes in urinary pyridinium crosslink excretion and plasma osteocalcin and growth hormone levels were measured at 3–5 week intervals in lambs from 2–22 weeks of age, in relation to changes in metatarsal length. There were close correlations between pyridinium crosslink excretion and plasma growth hormone levels and live weight gain, but no direct relationship was seen between the rates of excretion of the pyridinium crosslinks and linear bone growth. Plasma osteocalcin levels were correlated with linear bone growth rate up to about 12 weeks of age but, thereafter, showed no correlation despite a continued decline in bone growth rate. In the young lamb, daily pyridinium crosslink excretion represented 1.3–2.9% of that in the body, declining to 0.06% of pool size in adult sheep.

In vitro characterization and in vivo efficacy of a prostaglandin E2/poly(ortho ester) implant for bone growth promotion

Prostaglandin E 2 (PGE 2) is a known stimulator of bone growth, yet when systemically administered at efficacious levels there are serious side effects. It was hypothesized that local delivery of a low dose of PGE 2 would increase the rate of bone growth without systemic side effects. Biodegradable poly (ortho ester) (P (OE)) implants (4 mg, diameter = 2 mm, heights 1 mm) containing three different loadings of PGE 2 (0.81, 0.035 or 0.0032% PGE 2 w/w) were fabricated, characterized for in vitro release, and implanted in vivo in rat tibiae for 8 days. The PGE 2 release rate in vitro increased with increased initial loading of PGE 2; this increase was faster than predicted by a diffusional matrix release mechanism and was consistent with acid catalyzed P(OE) degradation in response to the PGE 2. In vivo, bone was examined at the end of the 8 day implantation period for new growth. These studies showed that the implants with the two highest loadings significantly enhanced (up to 3-fold) localized bone growth with no observable side effects in any of the treatment groups. This approach may be useful for enhancing bone growth in clinical situations which require bone augmentation or repair.

Failure of hyperfractionated radiotherapy to reduce bone growth arrest in rats

Purpose : Radiotherapy of the craniospinal axis is causing an age dependent growth arrest in children. The purpose of this paper was to examine in an animal model, whether hyperfractionated radiotherapy, given with twice daily fractions in conventional overall treatment time, would cause less growth arrest of the spinal column than a regular treatment schedule. Methods and Materials : The time-dose-fraction schedule for the treatment of the craniospinal axis of children with medulloblastomas was used as model for the treatment of the spine in rats. The entire spine of weanling rats received either 3570 cGy in 21 daily fractions of the 170 cGy, 5 times per week over 27 days, or 3630 cGy in 33 fractions of 110 cGy, given twice daily with 6-hr intervals over 21 days. Results : Both fraction schedules were isoeffective and caused a growth inhibition of 9.5%. The growth arrest was complete after 1870–2420 cGy. The alpha/beta ratio for the growing rat vertebrae was 3400 cGy. This result contrasts with the growth sparing effect observed with hyperfractionation of accelerated treatment schedules. Conclusion : Growing bone is a fast proliferating tissue. Hyperfractionation with 110 cGy BID compared to 170 cGy given once a day, has no sparing effect on bone growth in rats if given in conventional overall treatment time.

Determination of proliferative characteristics of growth plate chondrocytes by labeling with bromodeoxyuridine.

Postnatal bone growth occurs by the process of endochondral ossification in cartilaginous growth plates at the ends of long bones. The rate and extent of long bone growth is determined by a combination of chondrocytic proliferation, matrix production, and increase in chondrocytic height in the direction of growth during cellular enlargement. In this study, single pulse and/or repeated pulse labeling with the thymidine analog bromodeoxyuridine (BrdU) was used to study the role of cellular proliferation in controlling long bone growth. Variables studied included progression of the label over time following a pulse, and patterns and progression of the label over time following repeated pulse labeling for 24 and 48 hours. Examination was made of the proliferative characteristics of chondrocytes, the spatial pattern of cellular proliferation, and cell cycle kinetics. With respect to the spatial pattern of proliferative chondrocytes, results suggest that chondrocytes within a column are more synchronized with each other than are chondrocytes in different columns. This is consistent with the concept that each column represents a clonal expansion of a stem cell, which may proceed independently from adjacent columns. Despite this apparent heterogeneity, all chondrocytes in the proliferative zone complete at least one cell cycle in 24-28 hours. This estimate of the cell cycle time is significantly shorter than previous estimates of cell cycle times in similar growth plates. Our results also suggest that chondrocytes entering the cell cycle in the proximal part of the growth plate spend an average of 4 days in the proliferative cell zone, representing approximately four cellular divisions. After leaving the cell cycle, an additional 48 hours is required for the label to reach the terminal chondrocyte, which represents the time required to complete hypertrophy. These data are important when considering hypotheses concerning both the role of controls on proliferation in the determination of overall rate of long bone growth, as well as the interplay between proliferation and hypertrophy in regulating the overall amount of growth achieved by a given growth plate.

Testosterone alters duodenal calcium transport and longitudinal bone growth rate in parallel in the male rat.

Duodenal active calcium transport and longitudinal bone growth rate have been shown previously to be regulated in parallel by alteration of gonadal hormone status in sexually maturing female rats. The present study was designed to extend these observations to the sexually maturing male rat. Male rats were orchidectomized (ORX) and given Silastic implants containing either testosterone or estradiol at 6 weeks of age. At 9 weeks of age, duodenal active calcium transport was measured by the everted gut sac method and longitudinal bone growth rate was determined by tetracycline labeling. Decreases in body weight, longitudinal bone growth rate, duodenal calcium transport, and serum Ca and P were exhibited by ORX animals as compared with age-matched control animals. Testosterone administration to ORX animals resulted in an increase in body weight, longitudinal bone growth rate, duodenal calcium transport, and serum Ca and P as compared with ORX animals to a level not significantly different from that of age-matched control animals. Estradiol administration to ORX animals resulted in an additional decrease in body weight, although no significant effect on duodenal calcium transport, serum Ca, or P was noted as compared with ORX animals. There were no statistically significant alterations in the circulating levels of 1,25-dihydroxyvitamin D, parathyroid hormone, or osteocalcin in response to any of the experimental manipulations of gonadal status. These results indicate that, as in the female, gonadal hormone status affects intestinal calcium transport in sexually maturing male rats in parallel with changes in bone growth rate by mechanisms that are independent of circulating levels of 1,25-dihydroxyvitamin D.

A developmental constraint on the fledging time of birds

We examined the hypothesis that the rate of bone growth limits the minimum fledging time of birds. Previous observations in California gulls indicate that linear growth of wing bones may be the rate limiting factor in wing development. If bone growth is rate limiting, then birds with relatively long bones for their size could be expected to have longer fledging periods than birds with relatively short bones. We tested this by comparing the length of wing bones, relative to body mass, to the relative length of fledging periods among 25 families. The results support the hypothesis. A strong correlation exists between relative fledging period and relative bone length. Species which have relatively long bones for their body size tend to take longer to fly. In contrast, parameters that influence flight style and performance, such as size of the pectoralis muscle and wing loading, show little or no correlation with fledging time. The analysis also indicates that, when altricial and precocial species are considered together, bone length is more highly correlated with fledging time than is body mass or rate of increase in body mass during growth. These observations suggest that linear growth of bones does limit the growth of avian wings and that it is one of the factors that influences the fledging time of birds.

Regulation of duodenal insulin-like growth factor I and active calcium transport by ovariectomy in female rats.

There is a significant body of data that supports the concept that reproductive hormones in females have effects on duodenal calcium transport that are not mediated via altered circulating concentrations of 1,25-dihydroxyvitamin D (1,25(OH)2D). Previously, we have shown parallel alterations in duodenal Ca transport and longitudinal bone growth rate in sexually maturing female rats in response to ovariectomy and estradiol (E) treatment of ovariectomized (OVX) rats (OVX+E) without any change in circulating levels of 1,25(OH)2D or parathyroid hormone. Results are presented here from experiments designed to: (i) further explore the relationship between 1,25(OH)2D and ovarian status in the regulation of duodenal calcium transport, and (ii) determine whether OVX and E replacement alter circulating and duodenal levels of insulin-like growth factor I (IGF-I) that might be related to effects on Ca transport. Growth hormone, which has been shown to affect intestinal Ca absorption and vitamin D metabolism, is thought to act indirectly by stimulating IGF-I. Six-week-old female rats were OVX, given estradiol implants (OVX+E), and fed a diet containing either 0.5% or 0.1% Ca for 3 weeks. In both diet groups, the OVX animals exhibited a higher level of Ca transport, as measured by the everted gut sac method, than either the intact controls or the OVX+E group; there was no difference in calcium transport between the different diet groups. Although there was no difference in circulating levels of 1,25(OH)2D among the intact, OVX, and OVX+E groups fed either diet, animals fed the 0.1% Ca diet had higher circulating levels of 1,25(OH)2D than those fed the 0.5% Ca diet. There was no difference in duodenal levels of calbindin9K among intact, OVX, and OVX+E animals in either diet group, although the animals fed the 0.1% Ca diet had higher levels of calbindin9K than the animals fed the 0.5% Ca diet. In animals fed the 0.5% Ca diet, OVX resulted in elevated serum and duodenal levels of IGF-1, as compared with intact and OVX+E animals on the same diet. In animals fed the 0.1% Ca diet, there was no elevation of IGF-I in the OVX group relative to intact and OVX+E animals. These results lend additional support to the concept that alterations in duodenal active calcium transport that occur with alterations in ovarian hormones are not mediated by changes in serum levels of 1,25(OH)2D, but may be related to some factor related to growth, possibly IGF-I.

Limb deformity and metaphyseal abnormalities in thalassaemia major.

Regular bone survey radiographs have allowed identification of limb deformity and metaphyseal changes in several patients with thalassaemia major treated at the Adelaide Children's Hospital. Following the progression of limb deformity in five of these patients who were receiving human growth hormone therapy, the records of 25 thalassaemia patients were reviewed. Six patients had evidence of limb deformity, four of whom also had metaphyseal changes. Three additional patients had metaphyseal changes alone. Patients with either type of skeletal change shared similar characteristics, including younger age, earlier commencement of desferrioxamine therapy, better compliance and, in general, lower levels of ferritin. Females predominated in both groups. The frequency of sensorineural hearing loss was similar in affected and nonaffected groups and biochemical parameters, especially plasma calcium, phosphate, alkaline phosphatase, and zinc, which were normal in all patients. The cause of these skeletal changes is not clear; however, several potential factors need to be considered. Among these are focal marrow expansion in the metaphyseal region due to incomplete suppression of erythropoiesis and possible effects of desferrioxamine, including direct interference with bone growth, altered response of bone to inflammation or infection, and altered bone metabolism related to chelation of trace metals. While we can only speculate on aetiological factors, it is clear that human growth hormone therapy has resulted in exaggeration of deformity due to an increased rate of bone growth or decreased rate of mineralization of physeal cartilage. We believe that bone survey radiographs are useful in early identification of skeletal changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Linear bone growth of oMT1a-oGH transgenic male mice.

Linear bone growth was studied in male mice possessing a controlled ovine metallothionein 1a promoter-ovine growth hormone (oMT1a-oGH) transgene. Transgene expression was activated at weaning by the addition of 25 mM zinc sulfate to drinking water; transgenic and control mice received the zinc supplementation. The ulna, humerus, and tibia were excised at 10-day intervals until 130 days from control and from mice hemizygous for oMT1a-oGH. Bones from mice overexpressing growth hormone (GH) were 11-20% longer than those from controls (P less than 0.01) at 130 days. Transgenic mice exhibited both an enhanced rate of bone growth and a growth period of greater duration, i.e., the ulna, tibia, and humerus from oMT1a-oGH mice grew at an accelerated rate for an additional 20-40 days relative to the same bones from control mice. The bones from both groups were characterized by isometric growth patterns. Genetic size scaling revealed that the observed differences in bone growth were directly related to the mature size of the bone, suggesting that the bones possess an inherent growth pattern that is followed even in the presence of elevated GH.

Biomechanical repercussion of differential anti-anabolic effects of deflazacort and betamethasone on body and bone growth in rats

Biomechanical repercussion of differential anti-anabolic effects of deflazacort and betamethasone on body and bone growth in rats

Relationship between Nutrition and Bone Growth in Large and Giant Dogs

The pathogenesis of the osteochondrosis syndrome was studied in large and giant breeds of dogs. Spontaneous cases of osteochondrosis were examined in large breed dogs, and experimental disease was investigated in Great Dane puppies fed ad libitum or restricted diets until 6 mo of age. This investigation concluded that the primary lesion occurring in osteochondrosis of dogs from the large and giant breeds is an acquired pattern of osteopenic and biomechanically weak subchondral spongiosa that cannot provide adequate bony support for the articular cartilage of joints. Excessive biomechanical loading of the inadequately supported epiphyseal articular cartilage leads to secondary disturbances in the nutrition, metabolism, function and viability of the chondrocytes in the developing joint surface. The primary lesion in the subchondral spongiosa develops when overnutrition (ad libitum feeding) overstimulates skeletal growth and cancellous bone remodelling mechanisms in those breeds of dogs who already have an inherent capacity for rapid skeletal growth. The epiphyseal spongiosa of rapidly growing dogs of the larger breeds is inherently less dense and less strong per unit area than epiphyseal spongiosa of dogs from the smaller breeds. Overnutrition in dogs from the larger breeds exaggerates this tendency to create osteopenia by increasing the rates of skeletal growth and remodeling of the newly formed cancellous bone. Accelerated rates of bone growth and bone remodeling act in concert to product a pattern of epiphyseal spongiosa that is composed of fine trabecular systems that are spaced relatively far apart and that are ultimately less strong per unit area than in small breeds of dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Linear relationship between the volume of hypertrophic chondrocytes and the rate of longitudinal bone growth in growth plates

In this study, we tested the hypothesis that hypertrophic cell volume varies directly with the rate of longitudinal bone growth. The volume of hypertrophic chondrocytes (using stereological techniques) and longitudinal bone growth per 24 h (using oxytetracycline labeling techniques) were measured in the proximal and distal radial growth plates and the proximal and distal tibial growth plates of 21- and 35-day-old hooded rats and 21- and 35-day-old Yucatan pigs. We demonstrated a high coefficient of correlation (rats 0.98, pigs 0.83) between the final volume of hypertrophic chondrocytes and the rate of longitudinal bone growth over a wide range of growth rates and volumes of hypertrophic chondrocytes. In addition, we demonstrated a positive linear relationship between the rate of longitudinal bone growth and the final volume of hypertrophic chondrocytes. The slope of the regression line was different for rats than for pigs. The relationship was independent of the location of the growth plate in the animal and the age of the animal. The data suggest that mechanisms regulating volume changes in hypertrophic chondrocytes may exist and that chondrocytic volume increase is a major determinant of the rate of longitudinal bone growth. However, the relative contribution of cellular hypertrophy to longitudinal bone growth may be different in rats than in pigs.

Serum osteocalcin (Bone Gla-Protein), an index of bone growth in lambs. Comparison with age-related histomorphometric changes

In 96 normal male sheep, we studied the variations with age of serum osteocalcin (bone Gla-protein), measured with an assay specific for ovine osteocalcin. We compared serum osteocalcin with the main histomorphometric parameters of bone growth measured on the metacarpus of 20 normal lambs from birth to 90 days of age. Serum osteocalcin significantly decreased with age ( r = −0.70, p < 0.001), particularly during the first 90 days of life ( r = −0.85, p < 0.001). During this growth period, serum osteocalcin was significantly correlated with the appositional rate ( r = + 0.73, p < 0.001), the rate of longitudinal bone growth ( r = + 0.68, p < 0.002), the rate of production of chondrocytes in the growth plate ( r = + 0.60, p < 0.007), and the thickness of the growth plate ( r = + 0.79, p < 0.001). In low birth weight male lambs (growth-retarded animals), serum osteocalcin was significantly lower at birth when compared to normal lambs (271 ± 156 vs. 535 ± 169 μg/l, p < 0.001), and was also significantly correlated with histomorphometric parameters. We conclude that serum osteocalcin, which is already known as a sensitive and specific marker of bone formation, is also a sensitive biochemical marker of skeletal growth in normal and growth-retarded lambs. In addition, sheep appears as a valid animal for experimental studies on bone growth.

Effects of neonatal sympathectomy and capsaicin treatment on bone remodeling in rats

Bone metabolism may be influenced by the innervation of skeletal tissues. Neuropeptides such as vasoactive intestinal peptide, from sympathetic nerves, and calcitonin gene-related peptide, from sensory nerves, have been implicated as local modulators of bone metabolism. The effect of neonatal sympathectomy and of capsaicin-induced sensory denervation in rats was studied on the following: (i) the radial bone growth and apposition rate in tibiae (normal growth and modeling) and (ii) the percentage of periosteal surface of the mandible occupied by osteoclasts during induced remodeling. Neonate rats were treated with guanethidine, capsaicin, or appropriate vehicle. At seven weeks, maxillary molars were removed to induce remodeling on the buccal surface of the mandible. Animals were killed four days after surgery. Cross-sectional cortical area, medullary area, and periosteal apposition rate were measured by histomorphometry in ground sections of tibiae. The percentage of periosteal surface at the remodeling site occupied by osteoclasts (stained for acid phosphatase) was measured in frozen, undecalcified sections. There was no significant difference in cortical or medullary area or periosteal apposition rate in tibiae between each drug treatment and its control. However, the mandibular bone surface occupied by osteoclasts was increased 45.5% ( P ⩽ 0.005) in animals treated neonatally with guanethidine compared to controls. In contrast, the mandibular surface occupied by osteoclasts was decreased 21.2% ( P ⩽ 0.04) in animals treated neonatally with capsaicin compared to controls. The alteration of bone remodeling (osteoclast surface) by both treatments indicates that sensory and sympathetic nerves play a role in focal metabolism of bone.