Postmenopausal osteoporosis (PMOP) therapies are frequently evaluated by bone mineral density (BMD) gains against patients receiving placebo (calcium and vitamin D supplementation, a mild bone turnover-suppressing intervention), which is not equivalent to either healthy or treatment-naive PMOP. The aim of the present observational study was to assess the effects of TPTD treatment in PMOP (20 μg, once daily) at 6 (TPTD 6m; n = 28, age 65 ± 7.3 years), and 24 (TPTD 24m; n = 32, age 67.4 ± 6.15 years) months on bone quality indices at actively forming trabecular surfaces (with fluorescent double labels). Data from the TPTD-treated PMOP patients were compared with those in healthy adult premenopausal women (HC; n = 62, age 40.5 ± 10.6 years), and PMOP receiving placebo (PMOP-PLC; n = 94, age 70.6 ± 4.5 years). Iliac crest biopsies were analyzed by Raman microspectroscopy at three distinct tissue ages: mid-distance between the second label and the bone surface, mid-distance between the two labels, and 1 μm behind the first label. Mineral to matrix ratio (MM), mineral maturity/crystallinity (MMC), tissue water (TW), glycosaminoglycan (GAGs), and pyridinoline (Pyd) content were determined. Outcomes were compared by ANCOVA with subject age and tissue age as covariates, and health status as a fixed factor, followed by Sidak's post-hoc testing (significance assigned to p < 0.05). Both TPTD groups increased MM compared to PMOP-PLC. While TPTD 6m had values similar to HC, TPTD 24m had higher values compared to either HC or TPTD 6m. Both TPTD groups had lower MMC values compared to PMOP-PLC and similar to HC. TPTD 6m patients had higher TW content compared to HC, while TPTD 24m had values similar to HC and lower than either PMOP-PLC or TPTD 6m. Both TPTD groups had lower GAG content compared to HC group, while TPTD 6m had higher values compared to PMOP-PLC. Finally, TPTD 6m patients had higher Pyd content compared to HC and lower compared to PMOP-PLC, while TPTD 24m had lower values compared to PMOP-PLC and TPTD 6m, and similar to HC group. The results of the present study indicate that effects of TPTD on forming trabecular bone quality indices depend on treatment duration. At the recommended length of 24 m, TPTD restores bone mineral and organic matrix quality indices (MMC, TW, Pyd content) to premenopausal healthy (HC) levels.
- MeSH
- dospělí MeSH
- inhibitory kostní resorpce * farmakologie terapeutické užití MeSH
- kostní denzita MeSH
- lidé středního věku MeSH
- lidé MeSH
- os ilium patologie MeSH
- postmenopauzální osteoporóza * farmakoterapie patologie MeSH
- senioři MeSH
- teriparatid farmakologie terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
Prospective, controlled clinical trials in postmenopausal osteoporosis typically compare effects of an active drug with placebo in addition to vitamin D and calcium supplementation in both treatment arms. While clinical benefits are documented, the effect of this supplementation in the placebo arm and in clinical practice on bone material composition properties is unknown. The purpose of the present study was to evaluate these bone quality indices (specifically mineral/matrix, nanoporosity, glycosaminoglycan content, mineral maturity/crystallinity, and pyridinoline content) in patients that either received long-term vitamin D (400-1200IU) and calcium (1.0-1.5g) supplementation, or did not. We have analyzed by Raman microspectroscopy the bone forming trabecular surfaces of iliac crest in pre-treatment samples of a teriparatide study and the endpoint biopsies of the control arm obtained from the HORIZON trial. In general, the mineral/matrix ratio and the glycosaminoglycan (GAG) content was higher while nanoporosity, (a surrogate for tissue water content), the mineral maturity/crystallinity (MMC) and the pyridinoline (Pyd) content was lower in patients without long-term supplementation. Moreover, all indices were significantly dependent on tissue age. In conclusion, vitamin D and calcium supplementation is associated with altered mineral and organic matrix properties.
- MeSH
- aminokyseliny metabolismus MeSH
- analýza rozptylu MeSH
- fyziologická kalcifikace účinky léků MeSH
- glykosaminoglykany metabolismus MeSH
- kostní matrix účinky léků metabolismus MeSH
- lidé MeSH
- nanočástice chemie MeSH
- poréznost MeSH
- postmenopauzální osteoporóza farmakoterapie patofyziologie MeSH
- potravní doplňky * MeSH
- Ramanova spektroskopie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vápník farmakologie terapeutické užití MeSH
- vitamin D farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Teriparatide (TPTD) is the only currently available therapeutic agent that increases the formation of new bone tissue and can provide some remediation of the architectural defects in the osteoporotic skeleton. The use of teriparatide clinically is limited to 24 months. We review clinical findings during daily teriparatide treatment over time. Teriparatide appears to increase bone formation more than bone resorption as determined biochemically and histologically. Teriparatide exerts its positive effects on bone formation in two distinct fashions. The first is direct stimulation of bone formation that occurs within active remodeling sites (remodeling-based bone formation) and on surfaces of bone previously inactive (modeling-based bone formation). The second is an increase in the initiation of new remodeling sites. Both processes contribute to the final increase in bone density observed by non-invasive tools such as DXA. Remodeling is the repair process by which skeletal tissue is maintained in a young healthy state, and when stimulated by TPTD is associated with a positive bone balance within each remodeling cavity. It seems likely therefore that this component will contribute to the anti-fracture efficacy of TPTD. Teriparatide reduces the risk of fracture, and this effect appears to increase with longer duration of therapy. The use of novel treatment regimens, including shorter courses, should be held in abeyance until controlled clinical trials are completed to define the relative fracture benefits of such approaches in comparison to the 24-month daily use of the agent. Summary In patients with osteoporosis at high risk for fracture, the full continuous 24-month course with teriparatide results in improved skeletal health and outcomes than shorter time periods.
BACKGROUND: To investigate the mechanism by which strontium ranelate (SrR) inhibits the bone resorption, this study compared the effects of SrR and calcium on parathyroid hormone (PTH) and the biochemical marker of bone resorption (serum type 1 collagen cross-linked C-telopeptide, βCTX). METHODS: In 10 healthy young subjects, after overnight fasting, 1000 mg of elemental calcium and 2000 mg of SrR containing 600 mg Sr²⁺ were administered consecutively with a 1 week washout period. During the control period no drug was given. Fasting blood samples were drawn at baseline and throughout the next 5-h period. RESULTS: After the ingestion of either calcium or SrR, there was a significant increase in serum calcium and strontium concentrations, and a decrease in serum βCTX and intact PTH concentrations as compared to the baseline values (p<0.05). In the fasting subjects, no significant differences in the variable were found as compared to the baseline values. CONCLUSIONS: The decrease in PTH and the marker of bone resorption observed after the SrR administration is comparable to the decrease observed after the calcium administration in young adults.
- MeSH
- aplikace orální MeSH
- biologické markery krev MeSH
- dospělí MeSH
- kolagen typu I krev MeSH
- lidé MeSH
- mladý dospělý MeSH
- omezení příjmu potravy MeSH
- organokovové sloučeniny krev farmakologie MeSH
- parathormon krev MeSH
- peptidy krev MeSH
- referenční standardy MeSH
- regulace genové exprese účinky léků MeSH
- resorpce kosti krev MeSH
- thiofeny krev farmakologie MeSH
- vápník krev farmakologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
