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III.

Background and purposeThe primary event preceding the onset of symptoms in spontaneous osteonecrosis in the medial femoral condyle (SONK) may be a subchondral insufficiency fracture, which may be associated with underlying low bone mineral density (BMD). However, the pathogenesis of SONK is considered to be multifactorial. Women over 60 years of age tend to have higher incidence of SONK and low BMD. We investigated whether there may be an association between low BMD and SONK in women who are more than 60 years old.MethodsWe compared the BMD of 26 women with SONK within 3 months after the onset of symptoms to that of 26 control women with medial knee osteoarthritis (OA). All the SONK patients had typical clinical presentations and met specified criteria on MRI. The BMDs measured at the lumbar spine, ipsilateral femoral neck, and knee condyles and the ratios of medial condyle BMD to lateral condyle BMD (medial-lateral ratios) in the femur and tibia were compared between the two groups. The medial-lateral ratios were used as parameters for comparisons of the BMDs at both condyles.ResultsThe mean femoral neck, lateral femoral condyle, and lateral tibial condyle BMDs were between x% and y% lower in the SONK patients than in the OA patients (p < 0.001). The mean femoral and tibial medial-lateral ratios were statistically significantly higher in the SONK patients than in the OA patients.InterpretationA proportion of women over 60 years of age have low BMD that progresses rapidly after menopause and can precipitate a microfracture. These findings support the subchondral insufficiency fracture theory for the onset of SONK based on low BMD.

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NPY modulates the rat hypothalamic-pituitary-gonadal axis at both the adenohypophysial and central levels. Previously published studies have consistently shown elevations of GnRH content in the preoptic area (POA) and hypothalamus starting with the appearance of GnRH immunoreactivity around fetal day 12-14 until stabilization around the time of puberty. In the present studies, irNPY content of male and female rat hypothalami and POA was examined during days 0 to 36 of postnatal development. Hypothalamic irNPY content rose steadily from 4.54 +/- 0.19 ng/fragment (males) and 2.72 +/- 0.55 ng/fragment (females) at birth to 34.14 +/- 3.94 ng/fragment (males) and 46.79 +/- 6.16 ng/fragment (females) at day 36, corresponding approximately to the time of vaginal opening. A similar elevation of irNPY content was observed in the POA. At day 0, POA content was 1.91 +/- 0.18 ng/fragment (males) and 2.02 +/- 0.25 ng/fragment (females) and progressively increased to 42.26 +/- 3.94 ng/fragment and 41.33 +/- 3.72 ng/fragment by postnatal day 36. In subsequent investigations, hypophysial-portal and peripheral plasma irNPY was determined around the time of vaginal opening, revealing a surge in portal levels of irNPY which preceded the prepubertal LH surge. The progressive postnatal increase in hypothalamic and POA irNPY content culminating in a prepubertal surge of irNPY secretion into the hypophysial-portal circulation suggests involvement of this neuropeptide in reproductive development and the onset of puberty.

To clarify the regulatory mechanisms for the secretion of somatostatin (SRIF) from the hypothalamus, the effects of intracerebroventricular (i.c.v.) administration of growth hormone-releasing factor (GRF) and corticotropin-releasing factor (CRF) on SRIF secretion into hypophysial portal blood were examined in pentobarbital-anesthetized male rats. Neither the concentration of SRIF in portal plasma nor the secretion rate of SRIF was changed after i.c.v. administration of 0.9% saline. Administration of 10 ng or 5 µg human GRF i.c.v. produced a significant increase in the portal plasma concentration and secretion rate of SRIF. Likewise, 5 µg CRF significantly increased the portal plasma concentration and secretion rate of SRIF. These results suggest that the neuropeptides GRF and CRF centrally influence SRIF secretion into hypophysial portal blood.

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