James Richard Hartke

Three-dimensional microimaging (MRμI and μCT), finite element modeling, and rapid prototyping provide unique insights into bone architecture in osteoporosis

With the proportion of elderly people increasing in many countries, osteoporosis has become a growing public health problem, with rising medical, social, and economic consequences. It is well recognized that a combination of low bone mass and the deterioration of the trabecular architecture underlies osteoporotic fractures. A comprehensive understanding of the relationships between bone mass, the three‐dimensional (3D) architecture of bone and bone function is fundamental to the study of new and existing therapies for osteoporosis. Detailed analysis of 3D trabecular architecture, using high‐resolution digital imaging techniques such as magnetic resonance microimaging (MRμI), micro‐computed tomography (μCT), and direct image analysis, has become feasible only recently. Rapid prototyping technology is used to replicate the complex trabecular architecture on a macroscopic scale for visual or biomechanical analysis. Further, a complete set of 3D image data provides a basis for finite element modeling (FEM) to predict mechanical properties. The goal of this paper is to describe how we can integrate three‐dimensional microimaging and image analysis techniques for quantitation of trabecular bone architecture, FEM for virtual biomechanics, and rapid prototyping for enhanced visualization. The integration of these techniques provide us with an unique ability to investigate the role of bone architecture in osteoporotic fractures and to support the development of new therapies. Anat Rec (New Anat) 265:101–110, 2001.

Parathyroid hormone enhances fracture healing : A preliminary report

This investigation tested the hypothesis that daily parenterally administered parathyroid hormone (1-34) improves fracture healing. Twenty, 3-month-old, male Sprague Dawley rats weighing approximately 400 g each, underwent the production of closed, unilateral mid-diaphyseal femoral fractures. Animals were divided into two groups of 10; the animals received either a daily subcutaneous injection of delivery vehicle (0.9% saline) or 80 micrograms/kg parathyroid hormone. On Day 21 after fracture the animals were euthanized, the femurs were removed and subjected to biomechanical testing, bone densitometry (dual energy x-ray absorptiometry, peripheral quantitative computed tomography), and histologic examination. Treatment with parathyroid hormone resulted in statistically significant increases in callus area and strength. Histologic examination of the calluses showed an increase in the amount of new bone formed. No differences were observed in the weights of the animals or the sizes of the bones. Values obtained using dual energy x-ray absorptiometry and peripheral quantitative computed tomography indicate an increase in density in the parathyroid hormone treated fractures consistent with the histologic appearance and the findings of increased strength, although these bone density changes did not achieve statistical significance. These results suggest that parenterally administered parathyroid hormone (1-34) may enhance or accelerate normal fracture healing and support the concept that this hormone be tested clinically as a systemic treatment for fractures that are slow to heal.

Sex hormone effects in non-pregnant rat and human myometrium

OBJECTIVE To study effects of sex hormones on spontaneous contractility and on the effects of depolarizing agent potassium chloride (KCl), M-cholinoceptor and prostaglandin receptor agonists on non-pregnant rat and human uterine tissues. STUDY DESIGN Uterine rings from ovariectomized rats treated with sex hormones or placebo, and uterine strips from premenopausal and postmenopausal women were equilibrated in Krebs buffer (t=37 degrees C, pH approximately 7.4) for isometric tension recordings. Spontaneous contractile activity and contractions in response to KCl, eicosanoids, and acetylcholine were compared. RESULTS In tissues from ovariectomized rats, spontaneous contractility was increased, while KCl-induced contractions were decreased. Treatment with 17beta-estradiol, but not progesterone, inhibited spontaneous contractions, but potentiated KCl evoked contractions. Treatment with 17beta-estradiol did not influence responses to prostanoids in ovariectomized rats, while treatment with both sex hormones restored decreased the responses. Spontaneous contractility and responses to KCl were less in uterine tissues from postmenopausal versus premenopausal women. Hormone replacement therapy partly restored the responses to KCl, prostanoids, and acetylcholine. CONCLUSIONS Ovarian steroids modulate spontaneous contractile activity, responses to depolarization, prostanoids and M-cholinoceptor activation in non-pregnant rat and human uterine tissues in vitro.

Validation and application of an immunoradiometric assay for the determination of human parathyroid hormone fragment 1–34 in dog plasma following subcutaneous and intravenous administration

A method for the measurement of human parathyroid hormone fragment 1-34 (PTH1-34) in dog plasma was developed by modification of a commercially available immunodiometric assay (IRMA) designed for the determination of rat PTH1-34 in serum. Major modifications were made to the assay in order to circumvent significant problems encountered during the validation of the IRMA. PTH1-34 was found to be highly unstable in both rat serum and dog serum and plasma at room temperature, in contrast to literature reports. The addition of a protease inhibitor cocktail to serum or plasma samples was necessary to prevent in-vitro proteolytic degradation of human PTH1-34 prior to analysis. Additionally, plasma was chosen over serum as the sample matrix to expedite the separation of samples from cells, minimizing proteolytic degradation prior to the addition of cocktail. Finally, the reported 100% cross-reactivity between rat and human PTH1-34 was found to be only 65%; therefore, a human PTH1-34 standard was substituted for the rat standard. These modifications allowed the accurate measurement of human PTH1-34 in plasma obtained from dogs dosed intravenously and subcutaneously with human PTH1-34 using a commercially available kit.