David S. Weaver

Bone mass in female cynomolgus macaques: a cross-sectional and longitudinal study by age.

A cross-sectional study by age was designed to evaluate and describe the bone mineral content (BMC, g) and density (BMD, g/cm2) in a population of female cynomolgus macaques (Macaca fascicularis). Dual-energy X-ray absorptiometry was used to measure, in segments L2-L4 of the lumbar spine, the BMC (BMCs), BMD (BMDs), length, and total-body BMC (BMCTB) in 171 female monkeys ranging in age between 3.7 and 22.0 years. The animals were divided into three age groups: (1) young (<6.5 years, n=51); (2) adult (>6.5 years and <10.5 years, n=63); and (3) mature (>10.5 years, n=57). Young animals had a significantly lower (P<0.05) body weight and shorter trunk length than adult or mature animals. Young animals also had significantly less (P<0.05) BMCS, BMDS, and BMCTB than adult or mature animals, and had significantly shorter (P<0.05) lumbar spine vertebral segments than the other two groups. Longitudinally, 63 animals had repeated lumbar spine scans to examine changes over time. Young animals showed a positive and significant change (P<0.05) in BMCS and BMDS through time, whereas these parameters did not change in adult animals, and mature animals had a trend towards bone loss through time. Densitometric results suggested that peak bone mass in the lumbar spine was achieved by 9 years of age. Radiographic and dental criteria were developed to identify animals that had reached peak bone mass, and the combined radiographic and dental scoring system reliably identified animals 9 years and older. Female cynomolgus macaques 9 years old or older are recommended for investigations of bone remodeling and associated conditions, such as osteoporosis.

Effects of ovariectomy on iliac trabecular bone in baboons (Papio anubis)

SummaryBiopsies were collected from the left iliac crest of six adult female baboons, after which three of the animals were ovariectomized. Biopsies were collected from the right iliac crest six months later. Histomorphometric evaluation of the biopsies revealed consistent increases in fractional forming surface, appositional rate, and volume-based bone formation rate after ovariectomy. The data indicate that bone turnover is increased following ovariectomy in the baboon.

Effects of ovariectomy on vertebral trabecular bone in the cynomolgus monkey (Macaca fascicularis)

SummarySeventeen ovariectomized and twenty-one intact female cynomolgus macaques were examined for differences in vertebral trabecular bone volume. The ovariectomized group exhibited significantly less trabecular bone than the intact group (p<.005), 22 months post-ovariectomy. This finding encourages the use of the cynomolgus monkey as a model for the mechanism of bone loss in ovariectomy or postmenopausal osteoporosis.

The androgenic anabolic steroid nandrolone decanoate prevents osteopenia and inhibits bone turnover in ovariectomized cynomolgus monkeys

We examined the effects of nandrolone decanoate (25 mg im every 3 weeks) on bone mass, serum biomarkers, and bone histomorphometric endpoints in 52 female cynomolgus macaques randomized into four treatment groups: (1) sham-ovariectomized (sham); (2) ovariectomized + placebo for 2 years (ovx); (3) ovx + nandrolone decanoate for 2 years (Nan); and (4) ovx + nandrolone decanoate beginning 1 year after ovx (dNan). Serum alkaline phosphatase (ALP), osteocalcin, and tartrate-resistant acid phosphatase (TRAP) were assayed every 3 months, and X-ray densitometry of the lumbar spine was done every 6 months. Fluorochrome-labeled iliac biopsies collected at baseline and 1 year, and lumbar vertebrae and midshaft femur collected at 2 years, were evaluated histomorphometrically. Body weight increased over 50% with administration of nandrolone. After 2 years, ovx animals had lower spinal BMC and BMD than all other groups. Ovx animals also had higher bone turnover rates than all other groups, as indicated by higher levels of the serum and urine biomarkers, and by at least twofold higher label-based bone formation rates in the femur diaphysis and in both cancellous and cortical bone of the ilium and vertebral bodies. Nandrolone-treated animals had similar serum estradiol levels as the sham animals, presumably due to conversion of endogenous or exogenous androgens. The effects of nandrolone on bone in this experiment are consistent with estradiol action and may be attributable to the increased serum estradiol. Despite >50% higher body weight, nandrolone-treated, ovariectomized animals did not have higher bone mass than sham animals.

Accuracy and precision of lumbar bone mineral content by dual-energy X-ray absorptiometry in live female monkeys

SummaryDual-energy X-ray absorptiometry (DXA) was used to determine thein vivo bone mineral content (BMC) of lumbar vertebrae in 20 feral adult female cynomolgus macaques (Macaca fascicularis). The ash weight of the third lumbar vertebra (L3) was compared to the measured L3BMC of thein vivo DXA analyses. Correlation between the estimated L3BMC by DXA and the actual ash weight was significant (r=0.965,P<0.01); however, DXA methodology underestimated ash weight on the average of 6.2%. Correlation was significant between two sequentialin vivo DXA scans (r=0.988,P<0.001). Noninvasivein vivo DXA was a fast, precise, and effective method for measuring the lumbar BMC in female cynomolgus macaques.

Effects of the anabolic steroid nandrolone decanoate on plasma lipids and coronary arteries of female cynomolgus macaques.

In this study, we examined the effect of nandrolone decanoate, and anabolic steroid (AS), on plasma lipid concentrations and coronary arteries of female cynomolgus monkeys fed a moderately atherogenic diet. There were four treatment groups: (1) intact, sham-ovariectomized (n = 12); (2) ovariectomized (OVX) + placebo for 2 years (n = 15); (3) OVX + nandrolone decanoate for 2 years (n = 14); and (4) OVX + nandrolone decanoate beginning 1 year after ovariectomy (n = 11). Serial blood samples were analyzed for total plasma cholesterol (TPC), high-density lipoprotein cholesterol (HDL-C), very-low-density lipoprotein (VLDL-C) plus low-density lipoprotein (LDL-C) cholesterol, and estradiol. All animals were necropsied after 2 years, and the coronary arteries were evaluated. There was no difference in plasma lipid concentrations between groups (P > .05) at any time. Coronary artery atherosclerosis extent (plaque size) was significantly greater in the group administered nandrolone for 2 years compared with the intact sham-operated group (P < .05), but not with the OVX + placebo group. The groups administered nandrolone had significantly larger arteries than the other two groups. Lumen area was significantly larger in the group given nandrolone for 1 year compared with all other groups (P < .05). All artery effects remained after controlling the statistical analysis for body weight. Longer-term treatment with nandrolone resulted in increased plaque size, and therefore, the possible benefit of increased lumen area was compromised. The data also suggest that nandrolone was converted to estradiol, and this conversion also may play a role in the arterial and lipid effects observed.

Development of osteopenia in ovariectomized cynomolgus monkeys (Macaca fascicularis)

Spinal osteopenia that is due in part to failure to gain bone has previously been reported in ovariectomized nonhuman primates. In these studies, development of osteopenia over one year was followed by dual-energy x-ray absorptiometry in both domestically-reared and feral ovariectomized (OVX) and sham-ovariectomized (SHAM) cynomolgus monkeys. To promote development of absolute osteopenia, the domestically-reared animals were all older than nine years and were fed a diet containing 0.14% calcium for most of the experimental period. Both SHAM and OVX feral animals fed 0.6% calcium gained bone mass, with significantly lower rates of gain in SHAM monkeys. OVX domestically-reared monkeys lost bone during one year, while SHAM domestically-reared animals showed no significant change from baseline. Thus, relative osteopenia developed in both experiments, but only the domestically-reared animals developed absolute osteopenia. Nonhuman primates are the only animal model shown to develop absolute osteopenia after ovariectomy. These data suggest that absolute osteopenia develops after ovariectomy in monkeys with stable pre-ovariectomy bone mass which are fed a level of calcium comparable to that consumed by American women.

Erectile failure in cynomolgus monkeys with atherosclerosis of the arteries supplying the penis.

We evaluated by direction observation the sexual behavior of normal and atherosclerotic adult male cynomolgus monkeys (Macaca fascicularis) toward sexually receptive female cynomolgus monkeys. Marked deficits in erectile and ejaculatory function were found in the atherosclerotic monkeys. These animals were normal in other aspects of social and sexual behavior and had normal concentrations of circulating testosterone. At necropsy, histopathologic evaluation of the urogenital vasculature revealed atherosclerotic lumen obstruction of internal iliac, internal pudendal and penile arteries which apparently resulted in diminished in vivo capacity of these vessels to accommodate the large increases in blood flow required for the production of an erection. These findings provide further evidence for the existence of an association between atherosclerotic obstruction of the internal iliac, pudendal and penile arteries and the occurrence of erectile failure, and suggest the usefulness of the nonhuman primate as an animal model for clinical studies of atherosclerotic sexual dysfunction of man.

Two cases of facial involvement in probable treponemal infection from late prehistoric coastal North Carolina

This paper describes two late prehistoric burials from coastal North Carolina with cranial and postcranial lesions characteristic of treponemal infection. Each case exhibits facial lesions consistent with clinical reports of treponemal infection, but which have not previously been documented in these populations. The suite of facial lesions in one case and a mandibular lesion in the other serve to illustrate the variability inherent in treponemal infections.

Behavioral responses to ovariectomy and chronic anabolic steroid treatment in female cynomolgus macaques.

A pilot study was conducted to investigate the effects of ovariectomy on rates of aggressive and affiliative behavior, as well as body size, in 38 young adult female cynomolgus monkeys (Macaca fascicularis) living in isosexual social groups of four to five animals. In addition, we assessed the effects of nandrolone decanoate (an anabolic steroid used for postmenopausal hormone replacement therapy) on indices of aggression, submission, and body size. Animals were randomized into three experimental conditions: 1) sham ovariectomized, untreated (SHAM); 2) ovariectomized, untreated (OVX); and, 3) ovariectomized, treated with nandrolone decanoate for 24 months (NAN). Each individual was observed for 10 min, one to two times per month, and all instances of agonistic and affiliative behavior were recorded by means of focal animal sampling. Ovariectomized, untreated animals exhibited a two- to threefold increase in aggression compared to SHAM or NAN animals; F(2, 32) = 4.09, p = 0.026; however, the expression of prosocial or affiliative behaviors as measured by rates of grooming and initiating friendly behavior was unaffected. At an i.m. dose of 25 mg every 2 weeks, nandrolone decanoate caused a 60% increase in body weight of the animals compared to untreated intact and ovariectomized animals, F(2, 31) = 161.57, p < 0.0001.