Bone
Parathyroid hormone-related protein (PTHrP) is produced by a variety of cell types and shares many biological effects with parathyroid hormone (PTH) by binding to a common PTH/PTHrP receptor. PTHrP has been shown to be produced by breast cancer cells both in vivo and in vitro and is known to be an important mediator of hypercalcaemia of malignancy. In this study we have considered the possible role...
Synovial fluid macrophages (SF-M⌀) from patients with inflammatory arthritis can be activated by interferon-gamma (IFN-γ) to produce 1,25D 3 from 25-hydroxyvitamin D 3 (25D 3 ). The intracellular regulation of the 25D 3 -1α-hydroxylase (1-OHase) was investigated by studying the effects of IFN-γ (2.5-10 nM) in combination with factors that regulate signal transduction...
We report on a seven year study of bone density in 67 postmenopausal women. Using the same Molsgaard single photon absorptiometer ND1100A throughout, we measured the forearm bone mineral content (BMC). Four to ten (median 6) BMC measurements over periods of five to seven (median 6.9) years were obtained.The rate of bone loss calculated from the study population as a cross-section was high in younger...
Matrix metalloproteinases(MMPs) are a family of enzymes responsible for extracellular matrix degradation; their role in human bone remodelling has yet to be established. We have previously shown constitutive and inducible synthesis of MMPs by human osteoblasts in vitro and are now investigating the presence and localisation of MMPs and TIMP in human bone in situ using heterotopic bone as a model...
The aim of this study was to monitor the time course of changes in biochemical markers of bone turnover during fracture healing and to determine whether the time courses differed between markers. Eight postmenopausal women with distal forearm fractures, ages 58 to 83 years (mean 66 years) took part in the study. Blood and urine samples were collected within 36 hours of the fracture, and on days...
The actions of retinoids in developing limb tissues are well known. We investigated whether potential roles could exist for thyroid hormone (T 3 ), 1,25-(OH) 2 D 3 or glucocorticoids as developmental modulators in chick embryos using micromass culture assays. Mesenchymal cells from stage 21-27 chick embryo limb buds were plated at 1.5-2.0 10 5 per well in a 10μl...
Calcium intake and body mass are important determinants of attaining an optimum peak bone mass. To investigate the effect of these on body composition after the menopause, a group of normal healthy postmenopausal women (n=124), mean (SD) age 57.7 (2.6)yrs and menopausal age 7.8 (2.3)yrs were studied. Their mean body weight was 63.9 (7.4)kg and height 1.58(5.1)m and body mass index 25.5(2.2)Kg/m...
A variety of new markers of bone turnover have been described recently To investigate the ability of two of these to characterise patients with postmenopausal osteoporosis we have compared the levels of PICP and ICTP with histomorphometric findings.Fourty two women with postmenopausal osteoporosis underwent transiliac bone biopsy prior to commencement of treatment. At the same time blood was obtained...
We studied the safety and efficacy of fortified milk in young adults (median age 22.6 yr; range: 18-48 yr). Fortification increased the vitamin D 3 content from 0.3 μg/L to 12 μg/L, and elemental calcium from 1270 mg/L to 1525 mg/L. Volunteers (123) were recruited; 102 completed the trial. According to a double-blind protocol they were assigned in a random manner to receive either fortified...
This experiment was performed to characterise a new method to measure bone resorption rate in vivo, by studying the effects of known osteotropic agents.In growing rats, formation and resorption from the opposite sides of one cortex of the ulna cause a fluorochrome label to become closer to the resorbing surface. The change in this distance reflects the rate of bone resorption in film per day. Sixty...
Rickets is known to affect the mineralisation of forming teeth, however, few reports consider the delay of either individual teeth or the dentition as a whole. The developing teeth of ten archaeological specimens of known age (range 0.8 to 4.5 years) from the Spitalfields Collection that show bony changes associated with rickets, were investigated. Comparison of z-scores of tooth length and crown/root...
Osteogenesis imperfecta (OI) is often regarded as a severe disease of childhood. Frequently parents are given a pessimistic prognosis both for life and for physical abilities. No figures for life expectancy are available.We studied 743 OI patients resident in England and Wales. Patients who could not be assigned to one of the Sillence types were excluded as were patients with OI type II. For each...
Osteoblasts play a major role in the regulation of osteoclastic resorption. Recent studies have demonstrated production of chemokines by osteoblastic cells. Although these phagocyte-stimulating and pro-inflammatory cytokines act as chemoattractants and activators for other members of the haemopoietic lineage, their actions on osteoclasts have not been characterised.We found that MIP-1a and IL-8 powerfully...
Some nonunion fractures are infected with biofilm-forming Staphylococcus epidermidis (SE). We examined the effect of biofilms from several staphylococcal species on the in vitro proliferation of HOP. HOP were incubated with biofilm (5.0 mg/ml) at a range of dilutions for 48 hours. HOP were also cultured on coverslips/wells coated with biofilm. The effect of biofilms on HOP numbers, alkaline phosphatase...
Extracellular ATP acting through purinoceptors may be an important factor in the modulation of bone turnover. Classically, the presence of purinoceptors was established by pharmacological study in which the elevation of intracellular calcium was monitored in response to agonist binding. In this study we report for the first time the expression of mRNA for the P 2 U purinoceptor subtype...
Relationships between 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) levels in serum and synovial fluid (SF) and leukocyte cell number (polymorphs, lymphocytes and macrophages (M )) in SF were investigated in 59 patients with inflammatory joint disease. Patients were divided into 3 groups: A) SF:serum 1,25D ratio <1 (0.59±0.2, mean±SEM; n=44), B) SF:serum 1,25D ratio <1 (0.52±0...
Parathyroid hormone (PTH) and its (1-34) fragment are stimulators of bone turnover that have an anabolic effect increasing trabecular bone mass when administered intermittently by daily subcutaneous injections. Its clinical use in osteoporosis, however, has been limited by the concomitant increased bone resorption and deleterious effect on cortical bone. To evaluate if a treatment combining PTH...
Taxol (paclitaxel) is a promising anti-tumoral compound currently in clinical trials for the treatment of ovarian, breast and lung carcinomas as well as metastatic melanoma and leukaemia. It has a unique mechanism of action in that it promotes and stabilises microtubule formation, thus blocking tumour cell division at the G 2 -M mitotic phase. However, microtubules also play a role in cell...
In standard SEM imaging modes for porous bone, the trabeculae in the background may not be visible or distinguishable against the background, and porosity and relative distance cannot be directly demonstrated. We have studied the use of multiple detectors for forward-scattered and transmitted (TE) as well as backscattered fast electrons (BSE) in imaging osteoporotic cancellous bone. The samples...
Several bone-specific biochemical markers of turnover have recently been introduced. The aim of the study was to evaluate the clinical utility of these new markers in multiple myeloma. The study included 21 patients on standard treatment regimens who were studied cross-sectionally. They were 11 men aged 42 to 74 years, (mean 64.7) and 10 women aged 46 to 83 years, (mean 70.3). A control group...