Dual photon absorptiometry for bone mineral measurements using a gamma camera.

A gamma camera was equipped with a special collimator and arm assembly for bone mineral measurements with dual photon absorptiometry (DPA). The system was evaluated in vitro and in vivo and compared both with a rectilinear DPA and a dual energy X-ray (DEXA) system. All 3 systems showed a linear response in measurements of 4 vials, containing different amounts of hydroxyapatite.

The role of bisphosphonates in the prevention and treatment of osteoporosis.

Bisphosphonates are synthetic compounds that are taken up preferentially by the skeleton and suppress osteoclast-mediated bone resorption. There are structural differences among the various bisphosphonates that account for considerable differences in antiresorptive potencies and in activity/toxicity ratios. Bisphosphonates are given to patients with established vertebral osteoporosis, either intermittently or continuously, but controlled, long-term data are only available for intermittent regimens.

Quantification of adherent and nonadherent cells cultured in 96-well plates using the supravital stain neutral red.

In this study we present a rapid, simple, sensitive, inexpensive, and environment-friendly assay for determination of the number of adherent or nonadherent cells cultured in 96-well plates using the supravital stain neutral red. We describe a validation of the method and demonstrate its application to study the effects of hormones (i.e.

Bone mineral density in ambulant, non-steroid treated female patients with rheumatoid arthritis.

Bone mass measurements were performed in a group of 30 ambulant, non-steroid treated female patients with rheumatoid arthritis (RA) of relatively short duration (mean 4.9 years). The bone mineral density (BMD) of the lumbar spine and femoral neck was assessed by dual-energy x-ray absorptiometry (DEXA), and related to parameters of disease activity and severity.

Urinary collagen crosslink excretion: a better index of bone resorption than hydroxyproline in Paget's disease of bone?

The 24 h urinary excretion of the collagen degradation products pyridinoline (Pyr) and deoxypyridinoline (Dpyr) have been proposed as specific and quantitative indices of bone resorption. We compared the value of the urinary excretion of Pyr and Dpyr to that of hydroxyproline (OHP) in 11 patients with Paget's disease of bone before and during treatment with inhibitors of bone resorption, during admission to a metabolic ward and maintenance on a gelatin-free diet. Pyr and Dpyr excretion rates were significantly correlated with those of OHP (r = 0.

Bone metabolism in rheumatoid arthritis; relation to disease activity.

Biochemical parameters of bone metabolism were investigated in 105 ambulant, non-steroid treated patients with RA and compared with parameters of disease activity. Urinary calcium (Ca) and hydroxyproline (OHP) excretions, as parameters of bone resorption and serum alkaline phosphatase (AP), as a parameter of bone formation, were positively related to parameters of disease activity. Serum osteocalcin, another parameter of bone formation, was not related to parameters of disease activity.

Palliative pamidronate treatment in patients with bone metastases from breast cancer.

Purpose: An open, randomized study was performed to assess the effects of supportive pamidronate treatment on morbidity from bone metastases in breast cancer patients.

Patients And Methods: Eighty-one pamidronate patients and 80 control patients were monitored for a median of 18 and 21 months, respectively, for events of skeletal morbidity and the radiologic course of metastatic bone disease. The oral pamidronate dose was 600 mg/d (high dose [HD]) during the earliest study years, then changed to 300 mg/d (low dose [LD]) because of gastrointestinal toxicity.

Leukemia inhibitory factor inhibits osteoclastic resorption, growth, mineralization, and alkaline phosphatase activity in fetal mouse metacarpal bones in culture.

Leukemia inhibitory factor (LIF) has been reported to affect bone metabolism, but results are variable. We examined the effect of mouse recombinant LIF on osteoclastic resorption in fetal bone explants representing different stages of osteoclast development. In cultures of 17-day-old fetal mouse metacarpals in which only osteoclast progenitors and precursors are present, resorption (measured as 45Ca release) was significantly inhibited to 29.

Improved treatment of Paget's disease with dimethylaminohydroxypropylidene bisphosphonate.

A group of 89 patients with Paget's disease of bone were treated with different intravenous or oral doses of the nitrogen-containing bisphosphonate dimethylaminohydroxypropylidene bisphosphonate (dimethyl-APD). Biochemical remission was obtained in 82% of treatments, and in the rest a clear response was found. Oral dimethyl-APD was well tolerated, and a dose of 200 mg/day for 10 days was sufficient to induce remission in the majority of patients.

Physicochemical considerations in the development and prevention of calcium oxalate urolithiasis.

Calcium oxalate urolithiasis is very common in western societies. In recent years significant progress has been made in identifying and quantitating physico-chemical processes involved in calcium oxalate urinary stone formation. The ability of urine to inhibit the agglomeration of calcium oxalate crystals is an important protective mechanism against stone formation.

Modulation of tumour-induced bone resorption by bisphosphonates.

Tumour cells produce systemic or local factors which can stimulate osteoclast development and activity leading to increased bone resorption. The clinical consequences are bone pain, fractures and hypercalcaemia. Inhibitors of osteoclast-mediated bone resorption, such as the bisphosphonates, are now the treatment of choice for tumour-induced hypercalcaemia.

Disodium 1-hydroxy-3-(1-pyrrolidinyl)-propylidene-1,1-bisphosphonate (EB-1053) is a potent inhibitor of bone resorption in vitro and in vivo.

The ability of the new nitrogen-containing bisphosphonate disodium-1-hydroxy-3-(1-pyrrolidinyl)-propylidene-1,1-bisphosphona te (EB-1053) to inhibit osteoclastic resorption was examined in vitro and in vivo. Results were compared to those obtained with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (pamidronate or APD). In vitro, when tested in osteoclast precursor-dependent systems (fetal mouse metacarpals and a coculture system), EB-1053 suppressed 45Ca release effectively and was found to be about 10 times more potent than pamidronate (ED50 = 2.

Optimization of follow-up measurements of bone mass.

In bone densitometry, the precision of the instrument, the number of measurements and the time-points of the measurements are important criteria for monitoring bone mass changes. The most appropriate follow-up procedure can be determined by numerical comparison of various combinations of these three criteria. This can be done by computing the confidence interval of changes in bone mass.

Epi- and metaphyseal changes in children caused by administration of bisphosphonates.

Nitrogen-containing bisphosphonates (NCBs) are potent inhibitors of bone resorption and are used in the treatment of adults with various skeletal disorders. Little is known about their effects on the growing skeleton. The authors retrospectively studied the skeletal radiographs obtained in nine children before, during, and after NCB administration.

Paget's disease with osteolytic lesions: combining medical and surgical treatments.

A patient with extensive Paget's disease of bone presented with severe bone pain, hypercalcaemia and a large osteolytic lesion of the femur which developed during long-term therapy with etidronate. Treatment with pamidronate normalized serum calcium concentration and induced a complete biochemical remission. The osteolytic lesion was grafted with bone chips.

The effect of tissue type plasminogen activator (tPA) on osteoclastic resorption in embryonic mouse long bone explants: a possible role for the growth factor domain of tPA.

Osteoblasts produce proteolytic enzymes and their production is regulated by osteotropic agents. It has been suggested that these proteases play a role in bone resorption by removing the superficial collagenous layer from the bone matrix and indirectly inducing migration of osteoclast precursors towards the bone matrix. We examined the effect of the plasminogen activator tPA on osteoclastic resorption using 17-day-old mouse embryonic long bone explants representing different stages of osteoclast development, that is, radii containing already mature osteoclasts and metacarpals containing no mature osteoclasts but only osteoclast precursors/progenitors which are still confined to the periosteum.

Osteoclast formation together with interleukin-6 production in mouse long bones is increased by insulin-like growth factor-I.

Insulin-like growth factor-I (IGF-I) is a potent stimulator of bone formation. Whether this growth factor also induces bone resorption has not been studied in detail. We used two organ culture systems to examine the direct effect of IGF-I on bone resorption.

Regulation of parathyroid hormonelike protein production in cultured normal and malignant keratinocytes.

We have recently demonstrated that parathyroid hormone-like protein (PLP) production by cultured human squamous carcinoma cells (SCC) can be modulated by co-culture with fibroblasts. The interaction of SCC with fibroblasts, possibly occurring during the invasive phase of SCC, may be the stimulus for enhanced PLP production, thus contributing to the genesis of humoral hypercalcemia of malignancy in this type of cancer (Cancer Res 50:3589-3594, 1990). In the present study we show that the fibroblast-induced increase in PLP level in the medium of SCC-4 cells is paralleled by an increase in PLP messenger ribonucleic acid (mRNA) expression in these cells.

The use of bisphosphonates in the treatment of osteoporosis.

The efficacy of bisphosphonates in the treatment of conditions characterized by increased osteoclastic bone resorption has been established. Recent evidence indicates that these compounds are also effective in the treatment of patients with osteoporosis. Two main protocols have been tried.

Metabolic evaluation in stone patients in relation to extracorporeal shock wave lithotripsy treatment.

No information exists in the literature about the optimal time for metabolic evaluation of stone patients in relation to extracorporeal shock wave lithotripsy (ESWL) treatment. It is uncertain whether the presence of a stone, ESWL treatment itself or subsequent colic episodes influence the urinary risk factors. A prospective study was performed to determine the optimal period for metabolic evaluation.

Modulation of PTH-stimulated osteoclastic resorption by bisphosphonates in fetal mouse bone explants.

We examined the effects of the bisphosphonates Cl2MDP, APD, and Me2APD on osteoclastic resorption in the absence and presence of PTH using fetal mouse osteoclast-free bone explants cocultured with fetal liver as a source of osteoclast precursors. Results revealed qualitative and quantitative differences among the bisphosphonates tested. With Cl2MDP and APD fractional inhibition of resorption (measured as 45Ca release) in the presence of PTH was proportional to that obtained in its absence.

Regulation of the production of plasminogen activators by bone resorption enhancing and inhibiting factors in three types of osteoblast-like cells.

Production of proteolytic enzymes by osteoblasts is considered to be important for the initiation of osteoclastic bone resorption. We examined the production of tissue-type (tPA) and urokinase-type plasminogen activator (uPA) activity by three types of osteoblast-like cells (normal rat osteoblasts, rat and human osteosarcoma cells) using a quantitative spectrophotometric assay and a qualitative gel overlay technique. All 3 types of cells released both types of PA-activity into the medium, but normal rat osteoblasts released uPA probably in an inactive form.

Two distinct effects of recombinant human tumor necrosis factor-alpha on osteoclast development and subsequent resorption of mineralized matrix.

The multifunctional cytokine tumor necrosis factor-alpha (TNF alpha) stimulates osteoclastic resorption. It is not known which steps in osteoclast formation are affected by TNF alpha. We have investigated the effects of recombinant human TNF alpha (rhTNF alpha) on osteoclast development and osteoclastic resorption in two different in vitro resorption systems which are each characterized by a different stage of development of the osteoclast.