Cessation Of Bone Growth Research Articles

Complex ontogeny of sexual size dimorphism in a female-larger gecko: Implications of determinate growth for lizard body size and life-history evolution.

Ectothermic vertebrates such as reptiles were assumed to be indeterminate growers, which means that there is no terminal point in time or size for growth in their lifetime. In recent years, evidence for the determinate nature of growth in lizards has accumulated, necessitating a re-examination of models of their ontogeny and evolution of sexual size dimorphism (SSD). In the female-larger gecko Paroedura vazimba, we monitored post-embryonic growth over a period of 15 months. After hatching, females grew faster than males but also reached their final body size, that is, closed growth of their vertebrae, earlier than males. The closure of bone growth in females correlates with the onset of reproductive maturation. We compared this pattern with the previously minutely studied, male-larger species Paroedura picta, where we documented determinate growth as well. We propose a model to explain the evolutionary switches in the direction of SSD in lizards based on bipotential effects of ovarian hormones on growth. In this model, male growth is assumed to require no male-specific growth modifier, such as sex-limited hormonal regulators, while growth is feminized by ovarian hormones in females. Low levels of ovarian hormones can promote bone growth, but high levels associated with maturation of the reproductive organs promote senescence of bone growth plates and thus cessation of bone growth. We suggest that models on growth, life-history and evolution of body size in many lizards should acknowledge their determinate nature of growth.

Regulation of bone morphogenetic protein signalling and cranial osteogenesis by Gpc1 and Gpc3

From birth, the vault of the skull grows at a prodigious rate, driven by the activity of osteoblastic cells at the fibrous joints (sutures) that separate the bony calvarial plates. One in 2500 children is born with a medical condition known as craniosynostosis because of premature bony fusion of the calvarial plates and a cessation of bone growth at the sutures. Bone morphogenetic proteins (BMPs) are potent growth factors that promote bone formation. Previously, we found that Glypican-1 (GPC1) and Glypican-3 (GPC3) are expressed in cranial sutures and are decreased during premature suture fusion in children. Although glypicans are known to regulate BMP signalling, a mechanistic link between GPC1, GPC3 and BMPs and osteogenesis has not yet been investigated. We now report that human primary suture mesenchymal cells coexpress GPC1 and GPC3 on the cell surface and release them into the media. We show that they inhibit BMP2, BMP4 and BMP7 activities, which both physically interact with BMP2 and that immunoblockade of endogenous GPC1 and GPC3 potentiates BMP2 activity. In contrast, increased levels of GPC1 and GPC3 as a result of overexpression or the addition of recombinant protein, inhibit BMP2 signalling and BMP2-mediated osteogenesis. We demonstrate that BMP signalling in suture mesenchymal cells is mediated by both SMAD-dependent and SMAD-independent pathways and that GPC1 and GPC3 inhibit both pathways. GPC3 inhibition of BMP2 activity is independent of attachment of the glypican on the cell surface and post-translational glycanation, and thus appears to be mediated by the core glypican protein. The discovery that GPC1 and GPC3 regulate BMP2-mediated osteogenesis, and that inhibition of endogenous GPC1 and GPC3 potentiates BMP2 responsiveness of human suture mesenchymal cells, indicates how downregulation of glypican expression could lead to the bony suture fusion that characterizes craniosynostosis.

Femoral Angular Correction and Lengthening in a Large‐Breed Puppy Using a Dynamic Unilateral External Fixator

To report treatment of a large-breed puppy with combined distal femoral valgus and length deficit caused by partial distal physeal closure. Clinical report. Bernese Mountain Dog (4.5-month-old male). The puppy was admitted for evaluation of a progressive severe left pelvic limb lameness (grade 3/4) of 6-week duration. Distal femoral valgus and severe length deficit deformity were treated by acute angular correction using a closing wedge ostectomy and progressive rapid-rate callus distraction using a dynamic, telescoping unilateral External Skeletal Fixator (ESF) designed for people. After acute angular correction and a 3-day latency period, a mean linear distraction rate of 3 mm/day was maintained for 3 weeks. The dynamic ESF (dESF) was removed at 4 weeks, after a 1-week consolidation phase. The dESF was stable and functional during distraction and bone healing. Distal femoral valgus conformation improved 50° (from 41° to 91°) and femoral length increased 42 mm at dESF removal (from 158 mm to 200 mm; 27%). After cessation of bone growth, no valgus and minimal (6%) length deficit were detected. At 4, 5, 6, 12, and 24 months after surgery, the dog was walking, trotting, and galloping normally. Acute angular correction and progressive rapid-rate callus distraction using a unilateral dESF allowed satisfactory treatment of combined distal femoral valgus and length deficit in a large-breed puppy.

Effects of growth hormone on bone modeling and remodeling in hypophysectomized young female rats: a bone histomorphometric study

Growth hormone (GH) deficiency causes decreased bone mineral density and osteoporosis, predisposing to fractures. We investigated the mechanism of action of GH on bone modeling and remodeling in hypophysectomized (HX) female rats. Thirty female Sprague-Dawley rats at age 2 months were divided into three groups with 10 rats each: control (CON) group, HX group, and HX + GH (3 mg/kg daily s.c.) group, for a 4-week study. Hypophysectomy resulted in cessation of bone growth and decrease in cancellous bone mass. Periosteal bone formation decreased and bone turnover rate of endocortical and trabecular surfaces increased as compared to the CON group. GH administration for 4 weeks restored weight gain and bone growth and mitigated decrease in bone density after hypophysectomy. However, trabecular bone mass in the proximal tibial metaphysis remained lower in group HX + GH than in group CON. Dynamic histomorphometric analysis showed that bone modeling of periosteal bone formation and growth plate elongation was significantly higher in group HX + GH than in group HX. New bone formed beneath the growth plate was predominately woven bone in group CON and group HX + GH. Bone remodeling and modeling-remodeling mixed modes in the endocortical and PTM sites were enhanced by GH administration; both bone formation and resorption activities were significantly higher than in group HX. In conclusion, GH administration to HX rats reactivated modeling activities in modeling predominant sites and increased new bone formation. GH administration also increases remodeling activities in remodeling predominant sites, giving limited net gain in the bone mass.

Synergistic Effect of Vitamin K2 and Prostaglandin E2 on Cancellous Bone Mass in Hypophysectomized Young Rats

Hypophysectomy (HX) results in cessation of bone growth and cancellous osteopenia in rats. It has been reported that prostaglandin E2 (PGE2) improves cortical and cancellous bone mass in HX rats. The purpose of the present study was to examine whether combined administration of vitamin K2 and PGE2 would have a more beneficial effect on bone than single administration of either alone in HX rats. Forty-three female Sprague-Dawley rats, 6 weeks of age, were randomized by the stratified weight method into five groups: intact controls, HX, HX + vitamin K2 (30 mg/kg, p.o., daily), HX + PGE2 (0.83 mg/kg, i.m., 5 days a week), and HX + vitamin K2 + PGE2. The duration of the experiment was 4 weeks. There was a reduction in cancellous bone volume/total tissue volume (BV/TV) of the proximal tibial metaphysis and a reduction in total tissue area and cortical area (Ct.Ar) of the tibial diaphysis. Vitamin K2 did not affect cancellous BV/TV or Ct.Ar. On the other hand, PGE2 attenuated the loss of cancellous BV/TV in association with higher bone formation rate/bone surface (BFR/BS) and eroded surface (ES)/BS compared with intact controls. PGE2 also increased percent Ct.Ar compared with nontreated HX rats as a result of attenuation of a decrease in periosteal BFR/BS. Vitamin K2 had a synergistic effect with PGE2 on cancellous BV/TV as a result of the suppression of an increase in ES/BS observed by PGE2 treatment. These results suggested that PGE2 had an anabolic action on cancellous and cortical bone and that despite no apparent effect of vitamin K2 on bone, it had a synergistic effect with PGE2 on cancellous bone mass in young HX rats.

Development of the skeleton and feathers of dusky parrots (Pionus fuscus) in relation to their behaviour

A clutch of fve dusky parrots (Pionus fuscus) was observed from hatching to fully grown. They were examined radiographically from 16 to 45 days of age, a few days before...

Rates of growth and loss of bone mineral in the spine and femoral neck in white females.

This study characterizes the rates of growth and loss of bone mass as a function of age in white females. It combines longitudinal data from several studies of bone mass on healthy white female subjects ranging from age 6 to 90 years. Rates of change in bone area, bone mineral content (BMC) and bone mineral density (BMD) are estimated separately for the spine and the femoral neck of each individual using linear regression. The individual rates of change are then fitted as a nonparametric function of age using weighted moving averages, resulting in a curve of age-specific mean change as a function of age. When the curves of BMD were compared between the hip and the femoral neck, the cessation of bone growth and the onset of bone loss were found to occur at an earlier age at the hip than at the spine. No significant differences in the ages of maximum rates of growth or maximum loss were found between the two skeletal sites. This information will be useful for designing interventions to promote bone growth or retard bone loss.

Anabolic effect of prostaglandin E2 in bone is not dependent on pituitary hormones in rats.

Prostaglandin E2 (PGE2) is an anabolic agent of bone in vivo but the mechanism of its action still remains unclear. The aim of this study was to determine whether the effect of PGE2 on skeleton is mediated by pituitary hormones. Forty female, Sprague-Dawley rats were divided into four groups: baseline control (basal), age-matched intact control (CON), hypophysectomy (HX), and HX + PGE2 (2 mg/kg/day) with 10 animals in each group. The basal group was sacrificed at 2 months of age, and the remaining groups after 6 weeks of treatment. Cancellous and cortical bone histomorphometry was performed on double fluorescent-labeled 40 micron-thick sections of the proximal tibia and tibial shaft. Our results show that HX resulted in a cessation of bone growth, a decrease in cancellous bone volume, and cortical bone gain compared with the age-matched, intact CON rats. Compared with the HX group, the HX + PGE2 group had a significantly greater tibial bone density (mean +/- SE, HX + PGE2:1.595 +/- 0.007 versus HX:1.545 +/- 0.013), percent cancellous bone volume (21.4 +/- 2.0 versus 8.41 +/- 1.70), percent cortical bone area (87.2 +/- 0.85 versus 81.7 +/- 0.7), and ratio of cortical area to marrow area (7.14 +/- 0.56 versus 4.52 +/- 0.21). Increased bone masses by PGE2 in the HX animals were accompanied by an increase in the trabecular and endosteal-labeled surface and bone formation rate. The trabecular number and width were increased whereas trabecular separation was decreased in the HX + PGE2 group compared with the HX group (P < 0.05). PGE2 treatment also caused a decrease in the tibial endosteal eroded surface and medullar cavity of the HX animals. In conclusion, this study clearly demonstrates that PGE2 (2 mg/kg/day) in the HX rats increases both cortical and cancellous bones and improves trabecular architecture in the tibia after 6 weeks of treatment. These skeletal alterations are due to a stimulation of bone formation and a suppression of bone resorption activity. These findings suggest that the anabolic effect of PGE2 in bone is independent of pituitary hormones.

Effects of Growth Hormone and Estrogen Administration on Prevention of Osteopenia and Bone Growth in Hypophysectomized Young Rats † 503

Hypopituitarism results in a cessation of bone growth, a decrease in bone formation and cancellous bone volume in humans and animals, mechanism still remaining unclear. Growth hormone (GH) replacement to the hypophysectomized(HX) young rats restored the growth of long bone, but only partially prevented the loss of cancellous bone volume. This study is to examine the efficacy of GH with or without 17b-estradiol(E) on cortical and cancellous bones of the HX rats. 2 month old female Sprague-Dawley rats, were divided into basal(B), age matched intact control(AMC), HX, HX+GH(2.25mg/kg/day), HX+E(100ug/kg/wk) and HX+GH+E groups with 10 rats in each group. The basal group was sacrificed at two months of age and the remaining after 3 weeks of treatment. Prior to sacrifice, they were labeled with flurochrome chemicals at fixed time intervals for the estimation of mineral apposition rate(MAR) and bone formation rate(BFR). Our results showed that HX rats had atrophy of adrenal glands and uterus, cessation of systemic growth (tibial length, body and muscle weight) and a decrease in tibial and the 6th lumbar vertebral (L6) dry weight as compared to the B and AMC groups. The bone histomorphometry revealed that HX induced a decrease in periosteal MAR(0.2±0.4um/d vs AMC:3.1±0.5, P<0.05), periosteal BFR(1.4 ± 4.6um3/um2/d vs AMC:259±57, P<0.05) and a loss of cancellous bone (2.2±1.3% vs AMC: 14.5±3.4, P<0.05). GH administration to the HX rats restored systemic and bone growth, increased tibial (346±28mg vs HX:291±22, P<0.05) and L6(140±18mg vs HX: 120±13, P<0.05) dry weight, periosteal BFR(127±20um3/um2/d vs HX:1.4±4.6, P<0.05), and decreased cancellous bone loss (5.8±3.0% vs HX:2.2±1.3, P<0.05). The dosage of E used, prevented the cancellous bone loss in ovariectomized rats, but did not significantly prevent the cancellous bone loss in HX rats(4.0±3.0% vs HX:2.2±1.3,). E administration prevented uterine atrophy, but did not affect the systemic growth, bone growth or the periosteal BFR in the HX rats. The combined use of GH and E prevented the uterine atrophy, and increased the cancellous bone (7.0±2.6%) as compared to the GH treatment alone. In conclusion, this study clearly demonstrates the beneficial effect of E is diminished in HX rats and GH replacement is unable to restore the protection, however, the combined GH and E administration to HX rats has an additive effect to protect the bone mass, as compared to GH treatment alone.

Skeletal alterations in hypophysectomized rats: I. A histomorphometric study on tibial cancellous bone.

Hypophysectomy (HX) results in a cessation of bone growth and a decrease in bone metabolism. The purpose of this study is to examine the effect of HX on the static and dynamic histomorphometry of cancellous bone in the secondary spongiosa of the proximal tibial metaphysis in rats. Female rats, at 2 or 3 months of age, were HX and sacrificed at 0, 5 days, 2 and 5 weeks after the surgery. Age-matched intact rats served as controls. Cancellous bone histomorphometry was performed on double-fluorescent labeled, 30-microns-thick sections of the proximal tibia. Tartrate-resistant acid phosphatase histomorphometry was performed at 5 days on HX and control rats to evaluate the resorption in the metaphyseal bone. Although the intact rats gained in body weight, tibial length, tibial weight, and density after 5 weeks, these changes did not occur following HX. As compared to the basal group, HX resulted in a decrease in the density and dry weight of the metaphysis. The histomorphometric data showed that the cancellous bone volume and trabecular number of the secondary spongiosa were decreased and the separation was increased in the HX rats. The dynamic results showed that HX significantly decreased longitudinal growth rate and tissue-based bone formation and resorption. However, the bone surface-based eroded surface, labeled surface, the mineral apposition rate, and the bone formation rate did not differ between the intact and the HX rats at either the 2 or 5 weeks study. Five days after HX, the bone surface and tissue-based osteoclast surfaces were significantly lower in the HX than in the intact rats. Pituitary hormone deficiency results in cancellous bone loss. The bone loss is due primarily to the suppression of longitudinal growth-dependent bone gain and the inhibition of tissue-based bone turnover with a lower bone formation relative to bone resorption. The surface-based bone turnover is not affected.

The Relationship Between Muscle Growth and the Growth of Different Fiber Types in the Chicken

A relationship of muscle growth to fiber growth was investigated histochemically and allometrically in the chicken from 1 to 35 wk of age. Muscle fibers were classified into three types (I, IIA, and IIB) based on the reactivities for myosin adenosine triphosphatase and reduced nicotinamide adenine dinucleotide dehydrogenase. Fiber type composition widely varied in the four muscles examined in this study. Longus colli dorsalis contained all types. The Pectoralis was composed only of IIB fibers. The caudal portion of Femorotibialis medius was made up of Type I and IIA fibers. The caudal Iliotibialis lateralis and the cranial portion of Femorotibialis medius were composed of types, IIA and IIB. These latter two muscles showed a progressive increase of Type IIA fibers and decrease of Type IIB fibers with advancing age. Two processes controlling muscle growth were elongation and enlargement of muscle fibers. The elongation of muscle fibers stops by 15 wk of age, coincident with the cessation of bone growth. However, the enlargement of muscle fibers, the increase in diameter of muscle fibers, continued until 35 wk of age. The rate of enlargement of muscle fibers varied by muscle and fiber type. In general, greatest growth occurred in Type IIB fibers of hindlimb muscles.

Self-Regulation of Phosphate Intake in the Rat: The Influence of Age, Vitamin D and Parathyroid Hormone

Growing rats offered a choice of four pairs of diets, one low in P (0.1%) and the others containing 0.3, 0.6, 1.2 or 1.8% P, selected food mixtures in each case with nearly identical P contents (0.23–0.24%) (Ca:P = 2.2:1). Mature rats offered the same dietary choices exhibited less rigid diet selection but clearly preferred a diet higher in P (0.64–0.69%) (Ca:P = 0.9:1). Vitamin D-deficient animals selected less P than controls and parathyroidectomized rats severely limited their P intake. The increase in self-determined P consumption relative to Ca in mature rats is consonant with the greater decrease in the requirement for Ca associated with maturation and cessation of bone growth. Susceptibility to hypocalcemia in vitamin D deficiency and parathyroidectomy is a probable factor in the increased sensitivity to excess dietary P, which further depresses plasma Ca. These experiments confirm the existence of a feedback mechanism that regulates the voluntary consumption of P in accordance with physiological needs.

Sex differences in bone resorption: A scanning electron microscopic study of mouse parietal bones.

Bone resorption surfaces formed by osteoclasts can be identified as rough areas by scanning electron microscopy (SEM). In this study, the endocranial surfaces of mouse parietal bones were examined by SEM at 1, 4, 6, 8, 14 and 20 weeks of age in an attempt to understand the bone resorbing activity after the cessation of bone growth. On the inner surface of the parietal bones, the rough areas, composed of a group of 8 to 30 microns wide concavities, can be divided into two distinct groups (type I and type II). The surface of type I areas appeared irregularly rough and those of type II revealed feather, fire-flame, or wave-like patterns due to characteristic arrangements of the concavities. The rough areas occupying the inner surface of the parietal bones made up about 60% of the surface area at 1 week and about 5% at 4 weeks in both sexes. The rough areas were all type I at this age. After puberty, the rough areas in males occupied about 10% of the inner surface until 20 weeks and consisted of large type I and small type II areas. In females, the proportion of the rough areas increased after puberty and occupied about 40% of the endocranial surface at 14 and 20 weeks. The type I areas were much larger, increasing in size with age and eventually occupying a large proportion of the rough areas. The sex differences in the rough areas were reversed by gonadectomy. The results suggest that male and female gonadal products, possibly sex hormones, have respective inhibitory and stimulatory effects on the formation of bone resorptive surfaces, and may be responsible for the sex differences in the size and morphological features of the areas on the bone surfaces.

Long bone growth during prolonged intermittent corticosteroid treatment and subsequent rehabilitation

Immature A/J mice were treated for up to 7 weeks intermittent doses of triamcinolone hexacetonide and were thereafter allowed to recover for 7 weeks. Qualitative and quantitative morphological measurements were performed on the epiphyseal cartilage plate and diaphyseal bone of the humerus. By the third injection significant structural changes were noted in the cartilaginous tissue followed by a complete cessation of bone growth. The hormonal inhibitory effect on long bone growth lasted throughout the experimental period. However, at the end of the recovery period the length of the humerus was 96% of the normal. In contrast, the humeral width at midshaft and the width of its medullary cavity revealed slower recovery, achieving only 80% of the control values. Following rehabilitation, the growth of experimental epiphyseal plates exceeded that of nontreated animals as their width and the number of hypertrophic chondrocytes were 131% and 125% of their controls respectively. Thus, in A/J mice (a highly susceptible inbred strain of mice) intermittent (every four days) administration of a long-acting corticosteroid hormone arrested endochondral and periosteal bone formation; the former, however, underwent full recovery following the termination of the hormonal treatment.

Histopathology of amino acid deficiencies: VII. Valine

A synthetic valine-deficient diet was fed to young male rats for 22 days and to older male rats for 70 days. Both groups exhibited incoordination and circling as manifestations of central nervous system damage. Histologic examination of numerous tissues from the young rats established that the effects of the deficiency were both nonspecific and specific in nature. The nonspecific effects included atrophy of the testes and accessory sex glands, cessation of bone growth, severe thymic involution, loss of adrenal cortical lipid, and depression of the anterior pituitary acidophiles and gonadotropic basophiles. Specific alterations were present in the myocardium and brain. In the heart, the chief modifications included nuclear hypertrophy and cytoplasmic vacuolation. In the brain, the important changes included myelin degeneration of the vestibular and motor facial nerves, severe neuronal deterioration of the red nuclei, and moderate neuronal damage in the motor facial and deep cerebellar nuclei. The brains of the older rats, which were prepared only for estimation of myelin damage, showed more extensive myelin degeneration of the vestibular and motor facial nerves as well as the presence of myelin deterioration in the medial longitudinal fasciculus. In the pair-fed rats, tissue damage resulted from partial inanition. There was no “clinical” or histologic evidence of damage to either the heart muscle or to the nerve trunks and neurones of the central nervous system. No abnormalities were present in the tissues of the normal-control animals.

The Central-Graft Operation for Fusion of Tuberculous Knees, Ankles, and Elbows

The central-graft fusion operation, originally described by Hatt, in our experience has proved its value and has been most successful in the treatment of tuberculous knees and ankles, and reasonably successful in the treatment of tuberculous elbows. In children, especially, the operation is of supreme value because it offers a high percentage of successful joint fusions without causing cessation of bone growth. In the series of cases just reviewed, solid bone fusion by this operation was obtained in all of the fifteen children with tuberculosis of time knee. In the fusion of tuberculous knee joints in children it is of extreme importance to avoid allowing the patella to become attachmed to the femur at the anterior epiphyseal line; in our series of cases, this produced local cessation of growth with resulting marked genu recurvatum and shortening. In adults, the single-central-graft fusion operation for tuberculosis of the knee was successful in all of the nine patients operated on, although one patient required a second operation. In the ten adults who underwent the more conservative dual-central-graft operation for tuberculous knees, successful fusions occurred in eight patients and failure occurred in two. In the treatment of tuberculosis of the ankle, the central-graft fusion operation was performed in four children and five adults. Fusion was obtained in all of the patients, and we have had no failures. Also, it is of interest to know that this success was obtained without opening up of the diseased joints or erasion of the joint cartilages. In tuberculosis of the elbow, the operation was not quite so successful as it has proved to be in the cases of disease of the knee and ankle. Six patients with tuberculosis of the elbow were operated on, and although fusion was obtained in five of them with the use of the central graft, a second operation was required in two of the patients. The one failure remained a non-union, and the patient declined another operative procedure because he was content with the result that he had.