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PubMed1988

Transforming growth factor beta inhibits bone resorption in fetal rat long bone cultures.

TGF-beta 1 is a polypeptide that is abundant in bone matrix, is produced by bone cells, and modulates proliferation and differentiated functions of osteoblastic cells in vitro. TGF-beta 2 is a closely related polypeptide that was originally isolated from bone matrix. TGF-beta 1 has been shown previously to stimulate prostaglandin production in cultures of neonatal mouse calvariae, which causes these bones to resorb. We found similar effects with TGF-beta 2. In comparison, TGF-beta 1 and TGF-beta 2 failed to stimulate bone resorption in fetal rat long bone cultures during a 3-d incubation period in concentrations up to 50-100 times greater than those capable of inducing bone resorption in calvariae. Incubation with TGF-beta 1 for a further 3 d decreased bone resorption up to 30%. Moreover, bone resorption induced by the bone-resorbing agents IL 1 and 1,25-dihydroxyvitamin D3 was partially or completely inhibited by TGF-beta 1 and TGF-beta 2 during the second half of the 6-d incubation period. Inhibition of DNA synthesis with hydroxyurea inhibited bone resorption in long bones in a similar pattern to that seen with TGF-beta 1. The inhibitory effects of TGF-beta 1 and TGF-beta 2 on bone resorption in long bone cultures may therefore be due to inhibition of osteoclast precursor proliferation.

Animals↗
PubMed2001

The ratio of messenger RNA levels of receptor activator of nuclear factor kappaB ligand to osteoprotegerin correlates with bone remodeling indices in normal human cancellous bone but not in osteoarthritis.

The determinants of cancellous bone turnover and trabecular structure are not understood in normal bone or skeletal disease. Bone remodeling is initiated by osteoclastic resorption followed by osteoblastic formation of new bone. Receptor activator of nuclear factor kappaB ligand (RANKL) is a newly described regulator of osteoclast formation and function, the activity of which appears to be a balance between interaction with its receptor RANK and with an antagonist binding protein osteoprotegerin (OPG). Therefore, we have examined the relationship between the expression of RANKL, RANK, and OPG and indices of bone structure and turnover in human cancellous bone from the proximal femur. Bone samples were obtained from individuals with osteoarthritis (OA) at joint replacement surgery and from autopsy controls. Histomorphometric analysis of these samples showed that eroded surface (ES/BS) and osteoid surface (OS/BS) were positively associated in both control (p < 0.001) and OA (p < 0.02), indicating that the processes of bone resorption and bone formation remain coupled in OA, as they are in controls. RANKL, OPG, and RANK messenger RNA (mRNA) were abundant in human cancellous bone, with significant differences between control and OA individuals. In coplotting the molecular and histomorphometric data, strong associations were found between the ratio of RANKL/OPG mRNA and the indices of bone turnover (RANKL/OPG vs. ES/BS: r = 0.93, p < 0.001; RANKL/OPG vs. OS/BS: r = 0.80, p < 0.001). These relationships were not evident in trabecular bone from severe OA, suggesting that bone turnover may be regulated differently in this disease. We propose that the effective concentration of RANKL is related causally to bone turnover.

Adult↗
PubMed2002

Adjusting bone mass for differences in projected bone area and other confounding variables: an allometric perspective.

The traditional method of assessing bone mineral density (BMD; given by bone mineral content [BMC] divided by projected bone area [Ap], BMD = BMC/Ap) has come under strong criticism by various authors. Their criticism being that the projected bone "area" (Ap) will systematically underestimate the skeletal bone "volume" of taller subjects. To reduce the confounding effects of bone size, an alternative ratio has been proposed called bone mineral apparent density [BMAD = BMC/(Ap)3/2]. However, bone size is not the only confounding variable associated with BMC. Others include age, sex, body size, and maturation. To assess the dimensional relationship between BMC and projected bone area, independent of other confounding variables, we proposed and fitted a proportional allometric model to the BMC data of the L2-L4 vertebrae from a previously published study. The projected bone area exponents were greater than unity for both boys (1.43) and girls (1.02), but only the boy's fitted exponent was not different from that predicted by geometric similarity (1.5). Based on these exponents, it is not clear whether bone mass acquisition increases in proportion to the projected bone area (Ap) or an estimate of projected bone volume (Ap)3/2. However, by adopting the proposed methods, the analysis will automatically adjust BMC for differences in projected bone size and other confounding variables for the particular population being studied. Hence, the necessity to speculate as to the theoretical value of the exponent of Ap, although interesting, becomes redundant.

Adolescent↗
PubMed2006

Effect of treadmill gait on bone markers and bone mineral density of quadriplegic subjects.

Quadriplegic subjects present extensive muscle mass paralysis which is responsible for the dramatic decrease in bone mass, increasing the risk of bone fractures. There has been much effort to find an efficient treatment to prevent or reverse this significant bone loss. We used 21 male subjects, mean age 31.95 +/- 8.01 years, with chronic quadriplegia, between C4 and C8, to evaluate the effect of treadmill gait training using neuromuscular electrical stimulation, with 30-50% weight relief, on bone mass, comparing individual dual-energy X-ray absorptiometry responses and biochemical markers of bone metabolism. Subjects were divided into gait (N = 11) and control (N = 10) groups. The gait group underwent gait training for 6 months, twice a week, for 20 min, while the control group did not perform gait. Bone mineral density (BMD) of lumbar spine, femoral neck, trochanteric area, and total femur, and biochemical markers (osteocalcin, bone alkaline phosphatase, pyridinoline, and deoxypyridinoline) were measured at the beginning of the study and 6 months later. In the gait group, 81.8% of the subjects presented a significant increase in bone formation and 66.7% also presented a significant decrease of bone resorption markers, whereas 30% of the controls did not present any change in markers and 20% presented an increase in bone formation. Marker results did not always agree with BMD data. Indeed, many individuals with increased bone formation presented a decrease in BMD. Most individuals in the gait group presented an increase in bone formation markers and a decrease in bone resorption markers, suggesting that gait training, even with 30-50% body weight support, was efficient in improving the bone mass of chronic quadriplegics.

Absorptiometry, Photon↗
PubMed2002

Anterior cruciate ligament replacement: comparison of bone-patellar tendon-bone grafts with two-strand hamstring grafts. A prospective, randomized study.

BACKGROUND: The purpose of this investigation was to evaluate replacement of a torn anterior cruciate ligament with either a bone-patellar tendon-bone autograft or a two-strand semitendinosus-gracilis autograft to compare the results of clinical testing, patient satisfaction, activity level, functional status, and muscle strength. METHODS: Fifty-six patients with a torn anterior cruciate ligament were enrolled in a prospective, randomized, controlled study. Twenty-eight underwent reconstruction with a bone-patellar tendon-bone autograft, and twenty-eight were treated with a two-strand semitendinosus-gracilis autograft. Patients were followed for an average of thirty-nine months (range, thirty-six to fifty-seven months). At the time of final follow-up, twenty-two patients in each group were evaluated in terms of clinical test findings, patient satisfaction, activity level, functional status, and isokinetic muscle strength. RESULTS: The objective outcome of replacement of the torn anterior cruciate ligament with a bone-patellar tendon-bone graft was superior to that obtained with a two-strand semitendinosus-gracilis graft. At the three-year follow-up interval, the patients in whom a hamstring graft had been used had an average of 4.4 mm of increased anterior knee laxity compared with the laxity of the contralateral, normal knee, whereas the patients in whom a bone-patellar tendon-bone graft had been used had an average of 1.1 mm of increased knee laxity. Fourteen percent (three) of the twenty-two patients with a hamstring graft had a mild pivot shift, and 27% (six) had a moderate pivot shift. Only 14% (three) of the twenty-two patients with a bone-patellar tendon-bone graft had a mild pivot shift, and none had a moderate pivot shift. At the same follow-up interval, the patients in whom a hamstring graft had been used had significantly lower peak knee-flexion strength than those who had a bone-patellar tendon-bone graft (p = 0.039). In contrast, the two treatments produced similar outcomes in terms of patient satisfaction, activity level, and knee function (ability to perform a one-legged hop, bear weight, squat, climb stairs, run in place, and duckwalk). CONCLUSIONS: After three years of follow-up, the objective results of anterior cruciate ligament replacement with a bone-patellar tendon-bone autograft were superior to those of replacement with a two-strand semitendinosus-gracilis graft with regard to knee laxity, pivot-shift grade, and strength of the knee flexor muscles. However, the two groups had comparable results in terms of patient satisfaction, activity level, and knee function.

Adolescent↗
PubMed1998

Effects of moderate intensity exercise on tibial bone mass in mature ovariectomized rats: bone histomorphometry study.

The effects of moderate intensity exercise of different duration on the cancellous and cortical bone mass of the tibia were investigated in mature ovariectomized rats by bone histomorphometry. A total of twenty 23-week-old female Wistar rats were used in this study. Ovariectomy (OV) was performed on 15 animals, and they were divided into three groups of five animals each: an OV group, an OV + exercise for 30 min a day (EX30) group and an OV + EX60 group. The other 5 animals served as a sham-operated (SH) control group. The exercise consisted of treadmill running at 16 m/min and was performed 5 days a week for 12 weeks after the operation. After 12 weeks of exercise, bone histomorphometry was used to evaluate the cancellous bone (secondary spongiosa) of the proximal tibia and the cortical bone of the tibial shaft. The OV group showed a significant decrease in cancellous bone volume, with increased resorption and formation, compared to the SH group (P < 0.01). Although the OV + EX30 group showed a significant increase in cancellous bone volume, with decreased resorption and increased osteoblastic activity, compared to the OV group (P < 0.05), cancellous bone volume in the OV + EX30 group remained significantly lower than that in the SH group (P < 0.05). There was not a significant difference in cortical bone area between the OV group and the SH group, whereas the OV + EX30 group showed a significant increase in cortical bone area, with decreased resorption on the endosteal surface, compared to the OV group (P < 0.05). There were no significant differences in cancellous bone volume or cortical bone area between the OV group and the OV + EX60 group. The data suggest that moderate intensity exercise of appropriate duration may attenuate ovariectomy-induced cancellous bone loss and increase cortical bone mass in mature ovariectomized rats.

Animals↗
PubMed1999

[Bone tissue engineering seeded with bone marrow stromal cells].

OBJECTIVE: To assess the ability of bone graft substitutes to support the growth of cells in vitro and new bone formation in vivo. METHODS: The methods of tissue engineering were employed, the bone marrow derived stromal cells were seeded onto blocks of hydroxypatite (HA), cultured for two weeks, and implanted intermuscularly into the rabbit back muscle, scanning electron microscopy and undecalcified bone tissue sections were used to evaluate the the growth of cells in vitro and new bone formation in vivo. RESULTS: The stromal cells were attached to and grew upon the surface of the periphery HA pores, especially in the pores adjacent to the bottom of culture flasks. No cell growth was found on the surface of the central pores. At four weeks after implantation, new bone formation was observed in most HA blocks, almost all of the new bones were lamellar bone and deposited directly on the surface of the HA pore. Active osteoblast and osteoid were found on the surface of the newly formed bone, invasion of bone marrow was observed in some newly formed bone. CONCLUSION: Bone marrow stromal cells are potentially the source of seeded cells for use in bone tissue engineering, and the HA may be considered as a suitable scaffold for these cells. The findings may be useful for detailed researches on seeded cells, scaffold and implanting fashion of bone tissue engineering.

Animals↗
PubMedDate not supplied

Influence of implant design and bone quality on stress/strain distribution in bone around implants: a 3-dimensional finite element analysis.

PURPOSE: A 3-dimensional finite element analysis was performed to evaluate the influence of implant type and length, as well as that of bone quality, on the stress/strain in bone and implant. MATERIALS AND METHODS: Two types (screw and cylinder) and 4 lengths (9.2, 10.8, 12.4, and 14.0 mm) of titanium implants were buried in 4 types of bone modeled by varying the elastic modulus for cancellous bone. Axial and buccolingual forces were applied to the occlusal node at the center of the abutment. RESULTS: Regardless of load direction, maximum equivalent stress/strain in bone increased with a decrease in cancellous bone density. Under axial load, especially in the low-density bone models, maximum equivalent strain in cancellous bone was lower with the screw-type implant than with the cylinder-type implant. It was also lower with the longer implants than with the shorter implants. Under buccolingual load, equivalent stress/strain was influenced mainly by bone density. DISCUSSION: This study confirms the importance of bone quality and its presurgical diagnosis for implant long-term prognosis. Implant length and type can also influence bone strain, especially in low-density bone. CONCLUSIONS: The results of this study suggest that cancellous bone of higher rather than lower density might ensure a better biomechanical environment for implants. Moreover, longer screw-type implants could be a better choice in a jaw with cancellous bone of low density.

Biomechanical Phenomena↗
PubMed1984

The healing of segmental bone defects induced by demineralized bone matrix. A radiographic and biomechanical study.

UNLABELLED: We studied the effect of demineralized bone matrix on the repair of large femoral diaphyseal defects in a rat model by clinical, radiographic, and biomechanical methods. A standard procedure was first developed to create segmental defects that did not heal and in which non-union developed consistently. The effect of demineralized bone matrix on repair was then assessed by physical examination, serial radiographs, and biomechanical studies to determine deformation to failure, stiffness, torsional strength, and energy absorption. By twelve weeks, the defects that had been treated with demineralized bone matrix showed satisfactory repair and remodeling in most animals based on clinical and radiographic evaluation. The biomechanical studies demonstrated that the bone induced by demineralized bone matrix had an energy-absorption capacity and stiffness equal to those of intact rat femoral bone. The bone induced by demineralized bone matrix achieved 35 per cent of the torsional strength of normal bone and an increased capacity to deform under load. These biomechanical properties are similar to those observed in the early stages of normal fracture repair. CLINICAL RELEVANCE: An effective, readily available alternative to autologous bone-graft material would have a variety of clinical uses in orthopaedic surgery, such as augmenting fusions, aiding in the repair of high-risk fractures, and filling or bridging bone defects. Demineralized bone matrix may provide an important tool for these purposes by inducing bone that has the mechanical properties of fracture callus. This would reduce the morbidity associated with harvesting autologous bone and have an advantage over allografts or synthetic biomaterials that require incorporation by the host before they can support mechanical loads.

Animals↗
PubMed1998

The bone growing chamber: a new model to investigate spontaneous and guided bone regeneration of artificial defects in the human jawbone.

Spontaneous bone repair and regeneration of jawbone defects have been insufficiently studied in the dental literature. The present study analyzes a new human model designed to evaluate the basis for spontaneous bone regeneration in human jawbones. Hollow titanium cylinders, termed "bone growing chambers," were prepared with commercially pure titanium. Ten volunteers undergoing routine implant surgery were enlisted. A properly calibrated drill was used to prepare the bone-growing-chamber bed. The bone growing chamber was inserted inside the bone defect, and care was taken to submerge the cylinder at the level of the bone crest. After an adequate healing period, the bone growing chambers were retrieved with a small quantity of peripheral bone using a calibrated trephine bur. The retrieved specimens were processed to obtain thin undecalcified ground sections. The stable bone growing chambers showed bone tissue inside the growing space. The maturity of the regenerated bone was related to the time of removal. The bone growing chamber provides a well-defined space that is easy to prepare and to retrieve; its dimensions are always identical and it allows quantitative measurements of bone regeneration inside the chamber space.

Alveolar Process↗
PubMed1994

Interleukin-4 inhibits bone resorption through an effect on osteoclasts and proinflammatory cytokines in an ex vivo model of bone resorption in rheumatoid arthritis.

OBJECTIVE: To assess local bone resorption in the context of rheumatoid synovitis and its modulation by interleukin-4 (IL-4). METHODS: We developed an ex vivo model of bone resorption using juxtaarticular samples of bone obtained during joint surgery. We studied the histomorphometric parameters of bone resorption and the regulation of the production of IL-6, leukemia inhibitory factor (LIF), and the collagen cross-link pyridinoline, which is released during bone resorption in vivo. RESULTS: This was a sensitive and dynamic model of bone resorption. The bone samples produced high levels of pyridinoline and as much cytokine as synovium pieces obtained from the same joint. IL-4 induced a 70% reduction of IL-6 and LIF production by bone pieces and reduced pyridinoline levels. Histomorphometric studies performed on bone samples indicated a 35% increase in the mean total bone area after 7 days of treatment with IL-4. More importantly, with IL-4, osteoclasts were not detectable in the bone sections. CONCLUSION: The inhibitory effect of IL-4 on bone resorption extends our knowledge of its antiinflammatory properties and suggests that the inflammatory cytokine imbalance in rheumatoid synovium also contributes to defects in bone resorption in RA.

Adult↗
PubMed1991

Bone-particle-impregnated bone cement: an in vivo weight-bearing study.

To evaluate an experimental inorganic-bone-particle-impregnated bone cement, canine hip prostheses were implanted in dogs using a regular bone cement on one side and the experimental bone cement on the other. In a preliminary feasibility study, bone ingrowth into the resorbed bone-particle spaces was established 3 months after implantation in three dogs. In a more detailed study, twenty-eight (28) dogs were divided in four groups to delineate the effects of time on the phenomena of bony ingrowth. One month after implantation, active bone ingrowth into the bone cement was obvious. By 3 months postimplantation, the ingrowth appeared to have traversed the thickness of the bone-particle-impregnated cement. By the fifth month, most of the interconnected inorganic bone particles were replaced by new bone. At the end of a year, the ingrown bone was mature and negligible new bone activity was present. Biomechanical pushout tests closely corroborated the histologic observations. The maximum shear strength of the cement/bone interface of the experimental side reached 3.6 times that of the control side at 5 months postimplantation. No further improvements were seen at 12 months postimplantation. A viable bone/cement interface may result in a better orthopedic implant fixation system by combining the advantages of both cement for immediate rigidity and biological ingrowth for longterm stability.

Animals↗
PubMed2000

The effect of estrogen on the restoration of bone mass and bone quality in ovariectomized rats.

To evaluate the effect of estrogen on its ability to restore the bone mass and bone quality in ovariectomized rats by examining the changes of bone morphology and histomorphometry, 3-month-old rats were divided randomly into 4 groups: normal control, ovariectomized (OVX), sham-operated (Sham-O) and OVX plus estrogen (OVX + E2). Treatment initiated from the day 8 weeks after operation and continued for 12 weeks. Bone morphology and histomorphometry were examined afterwards. Results showed that comparing to control group, the trabecular bone in OVX appeared thinner and reduced in the amount. The connectivity between trabecula was decreased and the structure disordered. The free-end of trabecula was increased. The cavity of bone marrow enlarged. After treatment with estrogen, above changes improved remarkably by different degree, although did not reach the normal face. The bone histomorphometry results demonstrated that estrogen treatment increased bone mass and the amount of trabecula by 129% and 132% respectively (P < 0.05). The activity of bone resorption decreased significantly and the rate of bone formation increased to 203%. These results suggest that treatment of ovariectomized rats with estrogen can not only increase bone mass, also improve the bone structure and enhance the property of bone mechanics.

Animals↗
PubMed1997

Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases.

Adult↗
PubMed2000

Some osteocytes released from their lacunae are embedded again in the bone and not engulfed by osteoclasts during bone remodeling.

It is generally accepted that osteocytes derive from osteoblasts that have secreted the bone around themselves. Osteocytes are cells embedded in the lacunae in the bone, and they are characteristically in contact with other cells by many slender cytoplasmic processes in canaliculi. During bone remodeling, many osteocytes in the bone are released from their lacunae by osteoclasts; however it remains unclear what happens to these released osteocytes. The cortical bone of the rat mandibular body was used in this study. Mandibles were fixed, decalcified, and then embedded in Epon 812. Specimens were sectioned in the frontal direction into serial 0.5 microm-thick semithin or 0.1 microm-thick ultrathin sections, and then examined by light or transmission electron microscopy. Cells that fitted in the osteocytic lacunae with canaliculi extending to the bone were identified as osteocytes in this study. Among many osteocytes released by osteoclasts in cutting cones, there were osteocytes half-released from their lacunae. These cells fitted in their lacunae with canaliculi extending to the bone and showed developed cell organelles in the cytoplasm. In closing cones, many osteocytes were situated in the bone away from cement lines; however, there were half-embedded osteocytes in the bone formed on cement lines. These cells fitted in their lacunae with canaliculi extending to the bone formed below cement lines and showed developed cell organelles in the cytoplasm. These results show that half-embedded osteocytes in closing cones derive from half-released osteocytes in cutting cones. Osteocytes encircled by osteoclasts were sometimes observed on one section, but serial sections showed that these osteocytes fitted in their remaining lacunae in the bone on other sections. This shows that not all osteocytes released from their lacunae are engulfed by osteoclasts. Consequently, the present results suggests that some osteocytes released from their lacunae are embedded again in the bone and not engulfed by osteoclasts during bone remodeling.

Animals↗
PubMed1987

In vitro evidence that bone formation may be coupled to resorption by release of mitogen(s) from resorbing bone.

Bone-derived proteins have been shown to stimulate the proliferation of bone-forming cells and to increase the rate of embryonic bone formation in vitro. The current studies were intended to determine the tissue distribution of bone cell-active mitogen(s) in the embryonic chick, to determine the cellular origin and the target cell specificity of the bone cell-active mitogen(s) in embryonic chick bone, to determine whether the release of mitogenic activity from embryonic chick tibiae was proportional to bone resorption, and to compare mitogenic activities prepared from different skeletal sources, with respect to Mr, chemical stability, and mitogen activity kinetics. A bone cell-active mitogen(s) was identified in extracts of bone and cartilage but not in extracts of muscle, liver, intestine, or brain. (Mitogenic activity was determined as increased incorporation of 3[H]-thymidine into DNA in serum-free, calvarial cell cultures.) Together, the following three observations indicate an osteoblastic origin for the bone cell-active mitogen(s) in chick bone. First, the mitogen content of embryonic chick tibiae increased 4.5-fold, during eight days of serum-free in vitro growth (P less than .005). Second, conditioned medium (CM) from serum-free monolayer cultures of calvarial cells contained bone cell-active mitogen(s), but CM from parallel cultures of skin, liver, and intestinal cells did not. And, finally, the amount of bone cell-active mitogen(s) in calvarial cell CM was correlated with the amount of alkaline phosphatase (ALP) activity per cell, ie, an index of osteoblastic differentiation (r = .92, P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Recurrent bone regeneration in titanium implants. Experimental model for determining the healing capacity of bone using quantitative microradiography.

An experimental technique for quantitative assessment of bone repair was tested. The recurrent regeneration capacity of cortical bone was analyzed in consecutive 3 wk periods, using an osseointegrated titanium implant, the Bone Harvest Chamber (BHC), in the proximal tibial metaphysis of the rabbit. The BHC is a divisible implant penetrated by a canal into which newly formed bone tissue will grow during a 3 wk healing period. The newly formed bone tissue may easily be collected (harvested) without the animal being killed. After 3 wk, bone tissue can again be harvested, in principle, indefinitely. Intact harvested specimens were quantified by microradiography-videodensitometry, yielding a total specimen mass in mg aluminium equivalent. This unit correlated very well to a specimen dry weight (r = 0.996) and an average mineralized bone density (r = 0.937). The specimens were also examined by correlative histology. Three weeks after implant insertion, the chambers had become integrated in the bone tissue but the average bone mass varied widely, influenced by the surgical insertion trauma. Six weeks after insertion, the greatest average bone mass was found, indicating an intense ongoing osseointegration. The amount of bone regenerated at later harvests was fairly equal, indicating a stabilization of the implant bed to the repeat stimulus, i.e. harvesting. Bone regeneration differed significantly between animals, but also intraindividual variations, i.e. different amounts of bone formed in the same chamber, were observed.

Animals↗
PubMed1995

Age-related changes in IGFBP-4 and IGFBP-5 levels in human serum and bone: implications for bone loss with aging.

Osteoporosis develops because of an age-dependent imbalance between the rates of bone formation and bone resorption (i.e. bone formation rate is inadequate compared with bone resorption rate to maintain bone volume). With regard to the mechanism for the deficiency in bone formation, we propose that age-associated changes in the IGF system components contribute to an age-related decrease in the skeletal capacity for osteoblast cell proliferation. As a means of testing this hypothesis, we have measured serum levels of IGFBP-4 and IGFBP-5 since our studies have shown that the mitogenic actions of IGFs in bone cells are modulated by inhibitory IGFBP-4 and stimulatory IGFBP-5. By using newly developed and validated radioimmunoassays for measurement of IGFBP-4 and IGFBP-5, we found that the circulating level of IGFBP-4 increases with age while that of IGFBP-5 declines with age. In subjects from 23-87 years, serum IGFBP-4 concentrations showed a significant positive correlation with serum PTH while serum IGFBP-5 concentrations showed a significant positive correlation with IGF-I. These age-related changes in the serum levels of IGF system components are consistent with our previous findings of age-related decreases in the femoral cortical contents of IGF-I, IGF-II and IGFBP-5. Although the biological implications of the sequestration of IGFs in bone are unknown, we have hypothesized that the level of the IGFs in bone is a reflection of their integrated local secretion by osteoblasts. Based on our data, we now propose a model in which (a) underproduction of the stimulatory components and overproduction of an inhibitory component of the IGF system occur as a consequence of aging, and (b) these changes lead to an age-related decrease in the local (autocrine/paracrine) as well as the hormonal (endocrine) actions of the IGFs, which in aggregate could contribute to the decrease in osteoblast proliferation and the deficiency in bone formation. In conclusion, although our findings provide indirect evidence that age associated changes in IGF system components could lead to a deficit in bone formation, further studies are needed to demonstrate a cause and effect relationship between changes in bone cell production of IGF system components and the age-related uncoupling of bone formation from resorption.

Aging↗