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Biomedical subjects

D B Kimmel

Publications and source records attributed to D B Kimmel.

At least 37 records · Page 2Linked to original sources
PubMed1996

Correcting calcium nutritional deficiency prevents spine fractures in elderly women.

We tested the spine antifracture and bone sparing efficacy of 1.2 g/day of oral calcium as carbonate in two groups of elderly women, one with prevalent fractures (PF, n = 94) on entry and the other without (NPF, n = 103). It was a prospective randomized, double-blind, placebo-controlled trial in mostly rural communities in women over age 60 who were living independently and were consuming < 1 g/day of calcium. We obtained annual lateral spine radiographs and semiannual forearm bone density over 4.3 +/- 1.1 years and determined vertebral fractures by radiographic morphometry augmented by physician assessment. In the PF group, 15 of 53 subjects on calcium had incident fractures, compared with 21 of 41 on placebo (p = 0.023, chi2). Calcium did not reduce the rate of incident fractures in the NPF group. Those with a prevalent fracture on entry and not treated with calcium were 2.8 times more likely to experience an incident fracture than all others. Change in the forearm bone mass on placebo in the PF group was -1.24 +/- 2.41%/year compared with +0.31 +/- 1.80%/year on calcium (p < 0.001). In the NPF group, the difference was less: -0.39 +/- 2.08%/year versus 0.00 +/- 1.64%/year (p = 0.2). We conclude that in elderly postmenopausal women with spine fractures and selfselected calcium intakes of < 1 g/day, a calcium supplement of 1.2 g/day reduces the incidence of spine fractures and halts measurable bone loss.

Aged↗
PubMed1996

Bone mineral density and turnover following forelimb immobilization and recovery in young adult dogs.

The purpose of this experiment was to study changes in bone mass, structure, and turnover in the canine forelimb after unilateral immobilization and recovery. The right forelimbs of 14 adult mongrel dogs were immobilized for 16 weeks. Six dogs served as controls. Seven immobilized and three control dogs were euthanized at the end of the immobilization period. Recovery consisted of 16 weeks of kennel confinement followed by 16 weeks of treadmill exercise. Seven once-immobilized and three control dogs were euthanized at the end of the recovery period. Bone mineral density of both the proximal (PBMD) and central (CBMD) radius was determined by dual X-ray absorptiometry. Standard histomorphometric endpoints for bone mass and turnover were determined in the cancellous bone of the proximal radius. After immobilization, PBMD, CBMD, and trabecular thickness were lower in the immobilized limb than in either the contralateral or control limbs (P < 0.05). Only CBMD remained significantly lower (P < 0.05) after recovery. At the end of immobilization, bone formation endpoints were significantly higher in the immobilized limb than both the contralateral and control limbs. Bone turnover was also significantly lower in the contralateral limb than in the immobilized and control limbs. After recovery, all differences in bone turnover had resolved. Immobilization of 16 weeks duration caused an elevation in cancellous bone formation rate and reduced bone density in both cortical and cancellous bone. After 32 weeks of recovery, turnover abnormalities disappeared, cancellous bone normalized, but cortical bone mass remained low. Recovery of cortical bone from immobilization takes longer than recovery of cancellous bone.

Animals↗
PubMed1996

Scurvy results in decreased collagen synthesis and bone density in the guinea pig animal model.

The effect of severe ascorbic acid deficiency on bone remodeling and collagen synthesis was evaluated in a 21 day experiment, using the scorbutic guinea pig model. Animals (n = 6-7/group) were assigned to one of three groups: scorbutic, pair-fed ascorbic acid-replete, or ad libitum ascorbic acid-replete groups. After 2 weeks, scorbutic animals started voluntarily decreasing food intake and losing weight. By day 19-21, at which time bone and tissue samples were collected and analyzed, scorbutic animals decreased food intake to 46% of usual and lost 9% body weight. Serum 25OHD3, 1,25(OH)2D3, calcium, and albumin were significantly lower (p < 0.05) in the scorbutic animals than in the other groups. Bone mineral density and bone mineral content of the proximal and central femur were significantly lower in the scorbutic group than in the other groups (p < 0.05). Morphometric analysis of tibia indicated significantly lower bone volume, fewer and thinner trabeculae, and a thinner growth plate in the scorbutic group, compared to the pair-fed and ad libitum groups (p < 0.05). Osteoclast surface was about 60% higher in the scorbutic group than in the pair-fed and ad libitum control groups (0.05 < p < 0.10). Mechanical strength of the femur and lumbar vertebral body tended to be lower when bone mass was altered in the same group. Collagen synthesis of articular cartilage and tendons was lower in the scorbutic group than in the pair-fed or ad libitum groups (p < 0.05). In conclusion, scurvy but not food restriction, per se, results in alterations in bone mass and tissue collagen synthesis.

Analysis of Variance↗
PubMed1996

Long-term low ascorbic acid intake reduces bone mass in guinea pigs.

The effect of long-term (1 y) low to excess ascorbic acid (AA) intake on bone mass was evaluated using guinea pigs that were 12-14 d old at the start of the experiment. Dietary AA was low (0.15 g/ kg diet) (n = 7), normal (0.50 g/kg) (n = 8) or excess (10 g/kg) (n = 8). After 12 mo, total body bone mineral density (BMD, mg/cm2) and bone mineral content (BMC, g) were determined by dual energy X-ray absorptiometry. Histomorphometric analysis of the cancellous bone of the proximal tibial metaphysis was completed after in vivo dual fluorochrome labeling. Total body BMD of the low AA group was 4.9% lower (P < 0.05), and total body BMC was 12.4% lower (P < 0.05) than in the normal AA group. Total body BMD and BMC were similar in normal and excess AA groups and in the low and excess AA groups. Histomorphometric analysis indicated significantly greater (P < 0.05) double-labeled bone surface, mineralizing surface, and bone formation rate in the low AA guinea pigs compared with the normal AA animals. Thus, there was greater bone turnover in the low AA group than in the normal AA guinea pigs. No differences in histomorphometric endpoints existed between the normal AA and excess AA groups. Long-term AA deficiency, during the period of rapid growth and slower phases of skeletal maturation, resulted in bone abnormalities in adult guinea pig skeletons. Long-term dietary AA excess caused no such abnormalities.

Absorptiometry, Photon↗
PubMed1995

Partial maintenance of extra cancellous bone mass by antiresorptive agents after discontinuation of human parathyroid hormone (1-38) in right hindlimb immobilized rats.

The current study employs the immobilization (IM) rat model to induce osteopenia, parathyroid hormone (PTH) as the anabolic agent to restore bone mass, and 17 beta-estradiol, calcitonin, or risedronate as the maintenance agents to answer the following questions: How much cancellous bone loss occurs when PTH is withdrawn? Which antiresorptive or antiactivation agent maintains bone best? Ideally, what tissue-level histomorphometric conditions maintain added bone? Six-month-old female rats were treated with 200 micrograms PTH/day subcutaneously at 30 days post-IM for 75 days. Then PTH treatment was stopped and switched to a vehicle (no treatment), 10 micrograms calcitonin/kg/day, 10 micrograms 17 beta-estradiol/kg/day, or 5 micrograms risedronate twice weekly for another 15 days (early response) or 60 days (late response). The rats had their right hindlimb throughout the study. The current report deals only with the maintenance phase involving 92 animals. Bone histomorphometry was performed on the secondary spongiosa of the right proximal tibia metaphysis (PTM). Cessation of PTH treatment followed by vehicle administration for 15 days resulted in partial loss of trabecular bone area and thickness from stimulated bone resorption and the fall of all formation indices. By contrast, all three antiresorptive agents maintained the cancellous bone mass during the same period. However, after prolonged withdrawal of PTH for 60 days, we found that 17 beta-estradiol and calcitonin maintained the cancellous bone slightly better than no treatment, while risedronate partially protected it from the mechanostat-induced bone loss. The risedronate treatment retained 71% of the PTH-added bone while calcitonin retained 48%, estrogen 42%, and no treatment 32%. The favorable histomorphometry profile for maintenance was the sustained reduction in bone resorption and turnover and normal age-related bone balance. We concluded that 1) cessation of PTH treatment will result in the loss of two-thirds of the added bone in 60 days; 2) currently, risedronate at the dose level employed as a maintenance agent is far superior to 17 beta-estradiol or calcitonin because of its long retention in bone; however, a longer observation period might result in less difference; and 3) the ideal tissue-level histomorphometry continues depressing bone resorption and turnover and maintains a normal age-related bone balance. Furthermore, we found the "lose, restore plus add, and maintain (LRAM)" concept was successful in maintaining most of the PTH-induced extra bone by risedronate for 60 days. It was far superior to 17 beta-estradiol or calcitonin. Possibly the last two agents would be effective in maintaining a normal amount of bone but not in preserving an excessive amount of bone. Nevertheless, the current study further emphasizes that clinicians should consider using the LRM treatment strategy when they plan to treat osteoporosis with bone anabolic agents.

Animals↗
PubMed1994

Bone response to alternate-day mechanical loading of the rat tibia.

Mechanical loading of the living skeleton influences bone formation, mass, and strength. The primary purpose of the present study was to examine the influence of different loading schedules (days/week) on the bone response to external loading using an in vivo rat tibia four-point bending model. Three studies were conducted to (1) characterize the loaded region, (2) examine the variation of the response within the loaded region, and (3) test the response to different loading schedules. In all studies adult female retired breeder Sprague-Dawley rats were used (6 months, 285 g). First, the location of the loaded region during four-point bending was determined by radiogrammetry of 7 rats. Second, 5 rats were externally loaded for 8 of 10 days at 31 N, 36 cycles, and 2 Hz (1349 +/- 244 mu epsilon). The extent of labeled (forming) periosteal and endocortical surface in the loaded region was compared both among four serial sections from the same tibia and between the loaded and the contralateral tibiae. Finally, 50 rats were randomized into five groups: two nonloaded, control and sham, and three loaded, alternate day, Monday, Wednesday, and Friday, and daily. The rats were externally loaded for 3 weeks at 35 N, 36 cycles, and 2 Hz (1533 +/- 308 mu epsilon). The tibia and fibula were studied for labeled surfaces and mineral apposition rate. For adult female rats with tibial length 39 mm, the loaded region was located 3.5-14 (+/- 0.7) mm proximal to the tibia-fibula junction (TFJ).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Periosteal bone formation stimulated by externally induced bending strains.

The rat tibia four-point bending model is a new mechanical loading model in which force is applied through external pads to the rat lower limb. The advantages of the model are controlled force application to a well-defined bone, noninvasive external loading, and the addition of loads to normal daily activity. A disadvantage of the model is that the pads create local pressure on the leg at the contact sites. This study examined the differences in tibial response to bending strains and to local pressure under the pads. A total of 30 adult Sprague-Dawley rats were randomized into three external loading groups: bending, cyclic pressure, and static pressure. The right leg of each rat was externally loaded to create either bending or local pressure without bending; the left leg served as a control. Strains on the lateral surface averaged 1200 mu epsilon in compression during bending load application and < 200 mu epsilon in compression during pressure loading. Histomorphometric data were collected from three regions: the maximal bending region, under the loading pads, and outside the maximal bending region. In the maximal bending region, bending loads created greater mineral apposition rate (MAR) on the lateral surface and greater MAR and formation surface on the medial surface of loaded than control tibiae. The region under the bending pad was exposed to similar bending strains and showed the same pattern of increased MAR as sections from the maximal bending region. Cyclic pressure had no effect on periosteal MAR or formation surface. Static pressure increased MAR only on the lateral tibial surface. Bending stimulates bone formation in regions with the highest bending strains. Similar forces applied only in the form of pressure loading do not stimulate tibial formation either at the contact site or between loading pads. These results suggest that externally applied forces of moderate magnitude stimulate bone formation primarily as a result of increased bending strains, not local pressure at the contact site.

Animals↗
PubMed1994

Mechanical loading stimulates rapid changes in periosteal gene expression.

Although mechanical forces regulate bone mass and morphology, little is known about the signals involved in that regulation. External force application increases periosteal bone formation by increasing surface activation and formation rate. In this study, the early tibial periosteal response to external loads was compared between loaded and nonloaded contralateral tibia by examining the results of blot hybridization analyses of total RNA. To study the impact of external load on gene expression, RNA blots were sequentially hybridized to cDNAs encoding the protooncogene c-fos, cytoskeletal protein beta-actin, bone matrix proteins alkaline phosphatase (ALP), osteopontin (Op), and osteocalcin (Oc), and growth factors insulin-like growth factor I (IGF-I) and transforming growth factor-beta (TGF-beta). The rapid yet transient increase in levels of c-fos mRNA seen within 2 hours after load application indirectly suggests that the initial periosteal response to mechanical loading is cell proliferation. This is also supported by the concomitant decline in levels of mRNAs encoding bone matrix proteins ALP, Op, and Oc, which are typically produced by mature osteoblasts. Another early periosteal response to mechanical load appeared to be the rapid induction of growth factor synthesis as TGF-beta and IGF-I mRNA levels were increased in the loaded limb with peak levels being observed 4 hours after loading. These data indicate that the acute periosteal response to external mechanical loading was a change in the pattern of gene expression which may signal cell proliferation. The altered pattern of gene expression observed in the present study supports previous evidence of increased periosteal cell proliferation seen both in vivo and in vitro following mechanical loading.

Actins↗
PubMed1994

Cancellous bone behavior in hindlimb immobilized rats during and after naproxen treatment.

Temporary immobilization creates bone loss. The purpose of this investigation was to use an agent to protect the skeleton from bone loss bone during temporary immobilization. Eighty-nine 6-month-old retired breeder Sprague-Dawley female rats were used. Animals were randomly divided into six groups of equal numbers. Four groups were given drinking water from day 0, containing naproxen (100 or 200 mg/l). At day 7, half the animals in all groups had their right hindlimb immobilized. At day 49, half the immobilized rats and non-immobilized controls were sacrificed. The remaining rats were remobilized and the drug was stopped. At day 91, all remaining rats were sacrificed. Gastrocnemius and soleus muscle weights were determined. Right tibiae were analyzed for cancellous bone mass, bone structural and bone dynamic variables. At the close of immobilization, bone mass was lower in the right (immobilized) hindlimb of the immobilized group than in the non-immobilized group. Immobilized rats drinking 100 mg/l naproxen water had significantly higher bone mass in their immobilized limbs than did untreated immobilized rats, but all rats drinking 200 mg/l naproxen water had lower bone mass than controls. After 6 weeks of recovery, bone mass in the immobilized limb of untreated formerly immobilized rats improved, but remained below untreated never-immobilized rats. Formerly immobilized rats that had been treated with 100 mg/l naproxen water had normal bone mass after 6 weeks of recovery. Naproxen, an agent that mildly depresses activation frequency, prevents some of the transient bone mass and structural deterioration during temporary immobilization. Such treatment facilitates a more rapid return to normal bone mass, though not to normal structure. The more rapid recovery occurs because the difference from normal is less, not because of more rapid formation in recovering animals.

Analysis of Variance↗
PubMed1994

Current and investigational approaches for reversing established osteoporosis.

Osteoporosis is a disease of elderly women marked by low bone mass and increased risk of fracture. Though its prevalence can be reduced by timely estrogen replacement at menopause, many persons present with fragility fractures long after much bone has been lost. Osteoporotic subjects have low bone mass and poor structure but few or no metabolic abnormalities, such as ongoing bone loss, for treatment to normalize. The problem is to increase their bone mass and improve their bone structure. Today's major therapeutic approaches are summarized in Table 2. Ironically, they aim at stopping bone loss. Although preventing the skeleton of an osteoporotic person from growing weaker by stopping bone loss is better than allowing the process to continue, raising her to a significantly higher level of bone mass would be a better aim. Existing agents that stop bone loss by reducing turnover also increase bone mass mildly by filling the remodeling space. The result is a rise in bone mass during the first year or two of treatment to a new steady state 2% to 5% higher than baseline that persists throughout treatment. Fluoride increases spinal bone mass markedly. It decreases vertebral, but not hip fractures, but is associated with side effects and a nonresponse rate that makes pursuing other therapies attractive. Agents that upregulate bone mass through regulatory means have been tested in preclinical and a few clinical trials. PGE2 has been thoroughly tested preclinically. By studying PGE2, the field has learned that marked bone mass increases in the estrogen-deplete osteopenic skeleton are possible. The lack of bone specificity for PGE2 will probably limit its use to that of preclinical demonstration agent but leave open the possibility that less potent members of the prostaglandin family with better bone specificity might have promise as osteoporosis treatments. PTH or one of its analogues shows good promise for osteoporosis treatment. The wide availability of cheap PTH or proprietary analogues with similar activity will do much to speed its development. It increases bone formation and cancellous bone mass markedly. If PTH increases bone mass consistently in either large animal or human trials while causing only mild transient cortical bone mass declines, it can be a successful osteoporosis treatment agent. Bone growth factors appear to have much untapped potential for furthering the understanding of local control of bone processes and possibly for treating osteoporosis. Another possibility is biphasic therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1994

Effects of recombinant human interleukin-6 administration on bone in rhesus monkeys.

The role of interleukin-6 in the bone microenvironment is controversial. We studied the effect of recombinant human interleukin-6 (rhIL-6) administration on bone metabolism in 10 adult female rhesus monkeys (age 12-27 years). Monkeys received rhIL-6 (15 micrograms/kg/day) daily by subcutaneous injection for 28 days. Serum alkaline phosphatase, osteocalcin, and 24 h urinary calcium excretion were determined before, during (at weeks 2 and 4), and after (at week 6) treatment. Transilial biopsies (right and left) were obtained before treatment was initiated and just after the final (28th) dose at week 4. The serum alkaline phosphatase significantly increased at 2 and 4 weeks of rhIL-6 administration. Osteocalcin and urinary calcium excretion significantly decreased at week 2. Upon treatment with rhIL-6 significant reductions in OS/BS and Ob.S/BS were observed without changes in other static histomorphometry parameters. The reductions in urinary calcium excretion, serum osteocalcin, and the static bone parameters are consistent with an IL-6 induced reduction in bone formation or turnover. Whether this pharmacologic effect is relevant at the physiologic level remains to be determined.

Alkaline Phosphatase↗
PubMed1993

The health care status of the diabetic population as reflected by physician claims to a major insurer.

BACKGROUND: Conventional epidemiologic data suggest that diabetic patients use more health care resources than nondiabetic patients, yet overall health care use by diabetic individuals has never been fully quantitated. We took a new approach to this issue based on the actual economics of the provision of health care to diabetic insured individuals. METHODS: The claims records in the Mutual of Omaha Current Trends database, which contains information on more than 400,000 individuals, were surveyed to identify patients with diabetes and create the contrast population of nondiabetic patients by exclusion. International Classification of Diseases, Ninth Revision, Clinical Modification, codes and Physicians' Current Procedural Terminology, Fourth Edition, codes were used to determine all diagnoses recorded and all physician services rendered to the contrast populations. Age- and sex-adjusted comparisons were performed using Mantel-Haenszel procedures to determine an adjusted odds ratio (AOR). RESULTS: A total of 13,304 diabetic individuals and 388,053 nondiabetic individuals who received health care services from January 1, 1988, to January 1, 1989, were identified. Diabetic insured individuals constituted 3.1% of the overall insured population yet accounted for 8.3% of the charges (P < .01). Inpatient charges accounted for 81% of total diabetic charges but only 61.5% of total nondiabetic charges (P < .001). Diabetic insured individuals had twice as many physician office visits (AOR = 1.87; 95% confidence interval [CI], 1.79 to 1.96), with 2.5 times more physician hospital visits [AOR = 2.50; 95% CI, 2.27 to 2.75). However, the increases in physician care were not uniformly distributed across the diagnostic spectrum. The frequencies of well-established complications of diabetes, such as ischemic heart disease (AOR = 3.32; 95% CI, 3.12 to 3.53), peripheral vascular disease (AOR = 3.14; 95% CI, 2.79 to 3.53), and eye disease (AOR = 3.10; 95% CI, 2.94 to 3.27), were threefold higher in the diabetic group, with parallel increases in related medical services, such as cardiac catheterization (AOR = 3.02; 95% CI, 2.27 to 4.0), vascular surgery (AOR = 2.94; 95% CI, 2.64 to 3.27), and ophthalmologic procedures (AOR = 2.94; 95% CI, 2.72 to 3.18). In contrast, most diagnostic categories showed little or no increase. For example, the frequency of neoplasms (AOR = 1.11; 95% CI, 1.03 to 1.19) was minimally increased, and the associated procedural concomitants of therapeutic radiology (AOR = 0.81; 95% CI, 0.47 to 1.39) and chemotherapy (AOR = 0.98; 95% CI, 0.60 to 1.60) were not increased in the diabetic group. CONCLUSIONS: Our most important new finding is that diabetic patients have neither an elevated risk for a wide spectrum of diseases nor an increase in the receipt of physician services for diagnostic categories without increased risk, despite more frequent physician encounters. We provide real-world risk estimates that help in calculating the effect of offering specific insurance to diabetic individuals or including them in group health plans. The techniques we have developed to analyze computerized claims databases in this way may serve to better quantify the true impact of chronic diseases on the health care system.

Adult↗
PubMed1993

Effect of ovariectomy on bone response to in vivo external loading.

This study was undertaken to find whether the bone response to increased external loading (EL) of the tibia in rats is affected by estrogen depletion. Female Sprague-Dawley rats 6 months were randomly assigned to four groups of 10 each: sham ovariectomy without loading (Shm-XL), ovariectomy without loading (OVX-XL), sham ovariectomy with external loading (Shm-EL), and ovariectomy with external loading (OVX-EL). In vivo external loading by a four-point bending device was initiated 4 weeks after surgery. The right lower leg of each EL rat was loaded at 31.4 +/- 0.2 N for 36 cycles at 2 Hz every other day for 21 days (11 loading days). Mean in vivo induced strain was 1305 microstrain (mu epsilon) for Shm-EL rats and 1280 mu epsilon for OVX-EL rats. With external loading of the tibia, periosteal bone formation rose equally in Shm and OVX rats. Woven bone was present around the tibia or fibula in 60% of the loaded rats and none of the control rats. No loading response occurred either at the endocortical surface or in the cancellous bone of the proximal tibial metaphysis. After OVX, cancellous bone area in the proximal metaphysis declined and formation surface rose compared to Shm rats. Although periosteal and endocortical bone formation rose after OVX, no cortical bone loss occurred. We conclude that ovariectomy and attendant loss of endogenous estrogen do not change the cortical bone response to an external load of about 1300 mu epsilon in rats. However, these results may not predict the cortical bone response to loading in animals with Haversian remodeling that display estrogen-related loss of cortical bone.

Analysis of Variance↗
PubMed1993

A paradigm for skeletal strength homeostasis.

This article integrates engineering principles with skeletal biology to describe skeletal strength homeostasis. Skeletal strength revolves around its perceived mechanical usage. Mass, geometric properties, and fatigue damage burden are the principle determinants of structural strength. Bone cells form sensor and effector systems that monitor usage and adjust strength and stiffness by changing mass, geometric properties, and fatigue damage burden. The bone lining cell-osteocyte complex is the sensor; the bone modeling and remodeling systems are the effectors. Deformation and fatigue damage in bone are the signals received by the sensor. Accumulated energy in the sensor's cytoskeleton determines the rate at which the sensor sends messages to the effectors. The activity of both effector systems is proportional to the rate of incoming messages. Modeling raises bone strength and stiffness by improving geometric properties as it adds bone where customary deformation is greatest. Remodeling improves bone strength by replacing fatigue-damaged areas without mass changes. Bone removed during modeling and remodeling comes from sites where the impact on bone strength and stiffness is least. Hormones and agents alter the rigidity of the cytoskeleton and, thus, its capacity to deform and store energy. Osteopenic agents make it more rigid, causing detection of fewer deformations and transmission of fewer loading signals to the effector. Osteotropic agents decrease the rigidity of the cytoskeleton, causing detection of more strain events and transmission of more loading signals to the effector. Agent treatment thus establishes false conditions of disuse or hyperuse.

Biomechanical Phenomena↗
PubMed1993

Precision and accuracy for rat whole body and femur bone mineral determination with dual X-ray absorptiometry.

Precision and accuracy for rat whole body and excised femur bone mineral density (BMD) measurements were evaluated with two dual X-ray absorptiometry (DXA) systems. The 'small subject' mode on the Norland XR-26 (XR), and the 'ultra high resolution mode' on the Hologic QDR-1000/W(QDR) were used for the analysis. The whole body mode was only available on the XR. The lowest precision error for the whole body was found using a scan resolution of 1.0 x 1.0 mm and a scan speed of 15 mm/s. The scan spatial resolution of the femur measurement was approximately eight times higher on the QDR than on the XR. However, the XR allowed analysis of an arbitrary region of interest within the femur, which was not easily done with the QDR. Precision for the total femur measurement on the QDR (0.5-0.9%) was approximately two to four times superior to that of the XR (1.5-4.3%). The difference may be due to the superior scan resolution of the QDR. Bone mineral content and BMD on the QDR significantly declined with an increase of water depth (P < 0.001). No significant change was observed on the XR. Both DXA systems demonstrated an excellent correlation (r > or = 0.98) with ash weight under the scan conditions examined. The optimal scan condition for the excised femur measurement on the XR was obtained with 1.5-2.5 cm of perspex or water and a scan speed of 10 mm/s. For the QDR, we recommend scanning the rat femur with approximately 2.5 cm of perspex or water in terms of precision and accuracy.

Absorptiometry, Photon↗
PubMed1993

The effect of recombinant human (1-84) or synthetic human (1-34) parathyroid hormone on the skeleton of adult osteopenic ovariectomized rats.

The purpose of this study was to evaluate the dose-effect relationship of recombinant human PTH [hPTH-(1-84)] and synthetic human PTH [sPTH-(1-34)] for the skeleton of estrogen-deplete osteopenic rats. Ex vivo densitometry of regionalized whole femurs and histomorphometry of proximal tibial cancellous bone were the end points. Retired breeder female rats, aged 6-7 months, were used. Ten were killed at baseline, and the rest were ovariectomized (OVX). On day 42, a pre-PTH treatment OVX group was killed. The rest were then treated by daily sc injection with hPTH (0, 1.55, 15.5, or 155 micrograms/kg BW.day) or sPTH (0.55, 5.5, or 55 micrograms/kg BW.day) and killed on day 70. The level of cancellous bone mineral was lower in pretreatment OVX rats than at baseline. It was higher in rats treated with 15.5-155 micrograms/kg.day hPTH and 5.5-55 micrograms/kg.day sPTH than in pretreatment and vehicle-treated OVX rats. Cancellous bone volume was also lower both 42 and 70 days after OVX. Although hPTH did not affect cancellous bone volume, treatment with 5.5-55 micrograms/kg.day sPTH caused higher bone volume than in either pretreatment or vehicle-treated OVX rats. Trabecular number declined after OVX and did not change with PTH treatment. In contrast, trabecular thickness declined after OVX, but was higher after 15.5-155 micrograms/kg.day hPTH and 5.5-55 micrograms/kg.day sPTH treatment. In OVX rats, the amount of mineralizing surface was greater by day 42 and fell toward control levels by day 70. It was greater in rats treated with 15.5-155 micrograms/kg.day hPTH or 5.5-55 micrograms/kg.day sPTH than in vehicle-treated OVX rats. On a molar basis, sPTH was modestly more potent than hPTH. Osteoclast surface was not affected by PTH treatment. Treating estrogen-deplete osteopenic adult rats for 28 days with 15.5-155 micrograms/kg.day hPTH or 5.5-55 micrograms/kg.day sPTH increases trabecular thickness, but not trabecular number, to cause a rise in bone mass. The extent of mineralizing surface rises without a change in resorption surface. The marked rise in mineralizing surfaces suggests that extended in vivo treatment with PTH activates osteogenic precursor cells near once quiescent surfaces to become osteoblasts.

Animals↗
PubMed1992

Bone gain in young adult women.

OBJECTIVE: To test whether bone mass increases in healthy nonpregnant white women during early adult life after cessation of linear growth; and to test whether various self-chosen levels of physical activity and nutrient intake or use of oral contraceptives influences this increase in bone mass. DESIGN: Longitudinal prospective study of up to 5 years of 156 healthy college-aged women full-time students attending professional schools in universities in the Omaha, Neb, area. SETTING: University medical center. PARTICIPANTS: A convenience sample of healthy women students from Omaha-area professional schools. Any candidate with an illness, condition, or medication (except oral contraceptives) thought to affect general health or bone mass was excluded. INTERVENTIONS: None. OUTCOME MEASURES: Clinical and family histories of disease, particularly osteoporosis; oral contraceptive use; bone mineral densities of the spine, forearm, and total body by dual- and single-photon absorptiometry; estimates of nutrient intake by repeated 7-day diet diaries; and measures of physical activity using a physical activity monitor. RESULTS: The median gain in bone mass for the third decade of life, expressed as a percentage per decade, was 4.8% for the forearm, 5.9% for lumbar bone mineral content, 6.8% for lumbar bone mineral density, and 12.5% for total body bone mass (P < .0001 in all cases). By both bivariate and multiple regression analysis the rate of gain in bone density of the spine was negatively correlated with age and positively correlated with calcium/protein intake ratio and physical activity (multiple r = .31; P = .004). Bivariate analysis showed that use of oral contraceptives was associated with greater gain in total body bone mass (r = .31, P = .01). The estimated age when mineral acquisition ceased ranged from 28.3 years to 29.5 years at the several study sites. CONCLUSIONS: Gain in bone mass occurs in healthy young women during the third decade of life. Physical activity and dietary calcium intake both exert a positive effect on this bone gain. Use of oral contraceptives exerts a further independent positive effect. Changes in life-style among college-aged women, involving relatively modest increases in physical activity and calcium intake, may significantly reduce the risk of osteoporosis late in life.

Absorptiometry, Photon↗