Baseline bone turnover marker levels can predict change in bone mineral density during antiresorptive treatment in osteoporotic patients: the Copenhagen bone turnover marker study.

Anti-resorptive osteoporosis treatment might be more effective in patients with high bone turnover. In this registry study including clinical data, high pre-treatment bone turnover measured with biochemical markers was correlated with higher bone mineral density increases. Bone turnover markers may be useful tools to identify patients benefitting most from anti-resorptive treatment. INTRODUCTION: In randomized, controlled trials of bisphosphonates, high pre-treatment levels of bone turnover markers (BTM) were associated with a larger increase in bone mineral density (BMD). The purpose of this study was to examine this correlation in a real-world setting. METHODS: In this registry-based cohort study of osteoporosis patients (n = 158) receiving antiresorptive therapy, the association between pre-treatment levels of plasma C-telopeptide of type I Collagen (CTX) and/or N-terminal propeptide of type I procollagen (PINP) and change in bone mineral density (BMD) at lumbar spine, total hip, and femoral neck upon treatment was examined. Patients were grouped according to their pre-treatment BTM levels, defined as values above and below the geometric mean for premenopausal women. RESULTS: Pre-treatment CTX correlated with annual increase in total hip BMD, where patients with CTX above the geometric mean experienced a larger annual increase in BMD (p = 0.008) than patients with CTX below the geometric mean. The numerical pre-treatment level of CTX showed a similar correlation at all three skeletal sites (total hip (p = 0.03), femoral neck (p = 0.04), and lumbar spine (p = 0.0003)). A similar association was found for PINP where pre-treatment levels of PINP above the geometric mean correlated with a larger annual increase in BMD for total hip (p = 0.02) and lumbar spine (p = 0.006). CONCLUSION: Measurement of pre-treatment BTM levels predicts osteoporosis patients' response to antiresorptive treatment. Patients with high pre-treatment levels of CTX and/or PINP benefit more from antiresorptive treatment with larger increases in BMD than patients with lower pre-treatment levels.

Fracture-induced changes in biomarkers CTX, PINP, OC, and BAP-a systematic review.

To assess the time from fracture until bone turnover markers (BTM), which are biochemical markers reflecting in vivo bone formation and resorptive activity, have returned to a stable level since BTM have been shown to be at least as good as bone mineral density in monitoring the effect of anti-resorptive treatment in osteoporosis. This study searched for articles in PUBMED, CINAHL, Medline, EM-BASE, and Cochrane, and identified 3486 unique articles. These articles were screened based on predefined inclusion and exclusion criteria. Seven articles addressing time to normalization of either CTX, PINP, osteocalcin, or bone-specific alkaline phosphatase after a recent fracture were identified and these were analyzed qualitatively. CTX appeared to return to baseline within 6 months. PINP appeared to return to baseline within 6 months and interestingly dip below baseline after a year. Osteocalcin was elevated throughout the first year after a fracture, with most changes in the first 6 months. Bone-specific alkaline phosphatase (BAP) was increased for up to a year, however with a discrepancy between used assays. Seven studies were identified, showing CTX and PINP to return to baseline within 6 months. OC was elevated for 12 months. BAP was increased for up to a year. However, none of these studies had fasting patients and a long follow-up period with regular measurements. The studies could indicate that the BTM CTX and PINP have returned to baseline within 6 months; however, further studies are needed assessing pre-analytical factors while having a long follow-up. Bone turnover markers appear as good as or better than bone mineral density in monitoring the effect of anti-resorptive medication in osteoporosis. This study tries to identify the time from fracture until BTM are back at baseline. Most studies did not however take pre-analytical variation into consideration. Further research is therefore needed.

The bisexual brain: sex behavior differences and sex differences in parthenogenetic and sexual lizards.

The parthenogenetic lizard Cnemidophorus uniparens alternates in the display of male-like and female-like sexual behavior, providing a unique opportunity for determining the neuronal circuits subserving gender-typical sexual behavior within a single sex. Here we report a 6-fold greater [14C]2-fluoro-2-deoxyglucose uptake in the medial preoptic area of C. uniparens displaying male-like behavior in comparison with C. uniparens displaying female-like receptivity. The ventromedial nucleus of the hypothalamus showed greater 2DG accumulation in receptive C. uniparens than in courting C. uniparens. When a related sexual species (C. inornatus) was compared to the unisexual species, the anterior hypothalamus in C. inornatus males exhibited significantly greater activity.

Electrolytic lesions to the ventromedial hypothalamus abolish receptivity in female whiptail lizards, Cnemidophorus uniparens.

Lesions to the ventromedial hypothalamus (VMH) inhibit receptive sexual behavior in the whiptail lizard, Cnemidophorus uniparens, an all-female species. All lesions to the VMH that effectively abolished receptivity specifically damaged the dorsal lateral VMH, an area containing high concentrations of estrogen receptor in this species. These data further emphasize conservation of the VMH as a brain area critical to the expression of female sexual behavior in vertebrates.

Hormonal control of polymorphic and sexually dimorphic coloration in the lizard Sceloporus undulatus erythrocheilus.

This study investigated the influence of sex steroids on the expression of seasonally labile and sexually dimorphic coloration in the red-lipped plateau lizard. The responses of ventral blue and polymorphic facial coloration to exogenous steroid administration were assessed. Though facial color is usually dimorphic in nature, males and females did not differ in the degree to which they expressed facial coloration following administration of testosterone (T). Both sexes developed significantly more ventral blue coloration than controls, but a fundamental dimorphism in intensity, favoring males, was maintained throughout the experiment. These results indicate that facial coloration is under activational influence of T. The ventral blue coloration is probably organized at sexual maturation, thus manifesting the more vivid expression in males. Males of this subspecies are polymorphic for facial coloration. Administration of T did not cause any lizards to change hue, whether their color morph was yellow or orange or lacked the facial pigments altogether. The difference among color morphs is probably not controlled by differences in circulating steroid concentrations and is hypothesized to be under genetic control.

Catecholaminergic cells and fibers in the brain of the lizard Anolis carolinensis identified by traditional as well as whole-mount immunohistochemistry.

Using traditional as well as whole-mount immunohistochemistry, we described the location of tyrosine hydroxylase- and dopamine beta hydroxylase-positive cells and fibers in the brain of the lizard Anolis carolinensis. Major catecholaminergic cell groups were in the ependyma in certain ventricular regions, along the periventricular floor in the preoptic region, within the anterior hypothalamic and lateral hypothalamic areas, and in the mesencephalic tegmental region, locus coeruleus, nucleus of the solitary tract, vagal motor nucleus, and rhombencephalic reticular formation. Major catecholaminergic fibers, tracts and varicosities included tuberohypophysial, mesolimbic, nigrostriatal, isthmocortical, medullohypothalamic, and coeruleospinal systems. Although the catecholaminergic systems in A. carolinensis are similar to those in the brains of other lizards studied, there are a few species differences. Our information about A. carolinensis will be used to help localize the hypothalamic asymmetry in catecholamine metabolism previously described in this lizard.

Gonadotropin-induced ovulation in a reptile (Anolis carolinensis): histological observations.

Although much is known about morphological changes in the apex of the mammalian ovarian follicle prior to its rupture (ovulation), information about this process in nonmammalian vertebrates is limited to only a few species. We describe here the histological changes in the stigma of the lizard (Anolis carolinensis) ovarian follicle preceding FSH-induced ovulation. Females with a large vitellogenic follicle received two injections, separated by 7 hr, of either porcine FSH (25 micrograms) or saline, and then were sampled at 6, 9, 12, 15, 18, and 24 hr after the first injection. Thus, all but the 6-hr group received two injections. By 12 hr, about half of the FSH-treated females had ovulated, and most had ovulated by 15 hr. In contrast, only 1 of 40 control females ovulated. Large unovulated follicles were fixed and bisected through the circular stigma; one hemisphere was embedded in paraffin and stained with Mallory's trichrome, and the other was embedded in plastic and stained with toluidine blue. FSH treatment produced marked histological changes in the stigma region, as well as alterations in nonstigmal areas of the follicle. The membrana granulosa of control follicles consisted of a single layer of squamous, darkly staining granulosa cells. After FSH treatment, nonstigmal granulosa cells separated slightly, and their nuclei became more clear and assumed an oval shape; in the stigma, these cells became widely separated, with round, light-staining nuclei containing one or two prominent nucleoli. The nonstigmal theca of FSH-treated follicles was similar to that of control follicles except that collagen fibers were more dissociated. In the stigma, collagen fibers were widely dissociated, and the theca swelled, presumably due to accumulation of extracellular fluid. Abundant fluid accumulated in the stigma, especially between the granulosa cells and their basement membrane and between the tunica albuginea and the theca externa. These changes in the lizard stigma are similar to those reported in mammals except that no marked inflammatory response occurs in the lizard stigma. We hypothesize that the Anolis follicle undergoes preovulatory luteinization, and that the stigma exhibits ischemic necrosis before rupture.