Effects of Daily Treatment with Parathyroid Hormone on Bone Microarchitecture and Turnover in Patients with Osteoporosis: A Paired Biopsy Study

Abstract

We examined paired iliac crest bone biopsy specimens from patients with osteoporosis before and after treatment with daily injections of 400 U of recombinant, human parathyroid hormone 1-34 [PTH(1-34)]. Two groups of patients were studied. The first group was comprised of 8 men with an average age 49 years. They were treated with PTH for 18 months. The second group was comprised of 8 postmenopausal women with an average age 54 years. They were treated with PTH for 36 months. The women had been and were maintained on hormone replacement therapy for the duration of PTH treatment. Patients were supplemented to obtain an average daily intake of 1500 mg of elemental calcium and 100 IU of vitamin D. The biopsy specimens were subjected to routine histomorphometric analysis and microcomputed tomography (CT). Cancellous bone area was maintained in both groups. Cortical width was maintained in men and significantly increased in women. There was no increase in cortical porosity. There was a significant increase in the width of bone packets on the inner aspect of the cortex in both men and women. This was accompanied by a significant decrease in eroded perimeter on this surface in both groups. Micro-CT confirmed the foregoing changes and, in addition, revealed an increase in connectivity density, a three dimensional (

Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography

“…Results for the total hip site and the pelvis were intermediate between the spine and femoral shaft and can be explained by the mix of cortical and trabecular bone at these two ROI. An anabolic effect of teriparatide on human cortical bone was previously reported from bone biopsy studies, (13,14,16) although these were based on bone samples taken from the iliac crest and not all histology studies have shown such a pronounced effect on cortical bone. (15) There is a striking disparity between the present findings and the results of bone densitometry studies of the effects of teriparatide treatment at the spine and proximal femur.…”

“…(11) Many modern treatments for osteoporosis have a profound effect on bone remodeling, and studies of bone turnover have an important role in the evaluation of their effect on bone quality. (12)(13)(14)(15)(16) Bone biopsy with double tetracycline labelling is considered the gold standard for the direct assessment of bone turnover activity, but it is complex, invasive, and costly, and restricted to a single site, the iliac crest. (13)(14)(15)(16) The most commonly used and practical method is the measurement of bone turnover markers (BTMs) in serum and urine, which have the advantage of a large and rapid response seen in patients commencing treatment for osteoporosis.…”

“…(12)(13)(14)(15)(16) Bone biopsy with double tetracycline labelling is considered the gold standard for the direct assessment of bone turnover activity, but it is complex, invasive, and costly, and restricted to a single site, the iliac crest. (13)(14)(15)(16) The most commonly used and practical method is the measurement of bone turnover markers (BTMs) in serum and urine, which have the advantage of a large and rapid response seen in patients commencing treatment for osteoporosis. (9,11) Because BTMs provide information on the integrated response across the whole skeleton, they cannot provide insight into the changes that occur at specific sites such as the spine or hip or differentiate between the responses in trabecular and cortical bone.…”

“…Recombinant parathyroid hormone fragment rhPTH(1-34) (teriparatide) is an anabolic therapy approved for use in women and men with osteoporosis at high risk for fracture (5,28) that preferentially stimulates osteoblast over osteoclast activity, resulting in new bone formation and large increases in the rate of bone remodeling as measured by BTMs and bone histomorphometry. (11)(12)(13)(14)(15)(16) In this study, 18 F À PET imaging was used to assess the impact of teriparatide on regional bone metabolic response at the lumbar spine, pelvis, and proximal femur. The primary aims of the study were to evaluate the effect of 20 mg/day teriparatide on 18 F À plasma clearance at the lumbar spine in postmenopausal women with osteoporosis and compare the effects of teriparatide treatment on SUVs at the spine, pelvis, hip, and femoral shaft.…”

Modulation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors in a human osteoclast model in vitro

“…PTH is a potent stimulator of bone resorption and has a biphasic effect on bone formation. There is an acute inhibition of collagen synthesis when dosed with high concentrations of PTH, but prolonged intermittent administration of this hormone produces increased bone formation, a property for which it is currently being explored clinically as an anabolic agent (Dempster, 2001) 1,25-Dihydroxy vitamin D has its greatest effect on intestinal calcium and phosphate absorption, but it also has direct effects on bone and other tissues. Vitamin D is critical for the differentiation of both osteoblasts and osteoclasts and can stimulate bone resorption and formation under some experimental conditions (Raiz, 1999).…”