Article

Strontium Is Incorporated Into Mineral Crystals Only in Newly Formed Bone During Strontium Ranelate Treatment

Journal of Bone and Mineral Research, v.25, 968-975 (2010) DOI:urn:ISSN:0884-0431
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    Article: Potential mechanism of alendronate inhibition of osteophyte formation in the rat model of post-traumatic osteoarthritis: evaluation of elemental strontium as a molecular tracer of bone formation.
    A Panahifar, W P Maksymowych, M R Doschak
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    ABSTRACT: To employ elemental Strontium as a tracer of bone turnover, in the presence (or absence) of the bisphosphonate drug Alendronate, in order to spatially map osteophytogenesis and other bone turnover in rats developing post-traumatic secondary osteoarthritis (PTOA). PTOA was induced in rats by medial meniscectomy surgery. We utilized in-vivo microfocal computed tomography (CT) to follow bony adaptations in groups for 8 weeks after surgery, either with or without alendronate treatment. Electron probe microanalysis (EPMA) was used to detect Strontium incorporation in mineralizing tissues. Histologic studies were conducted on the same samples using Safranin-O/fast green and Tetrachrome staining of decalcified sections to examine articular cartilage health and osteophyte formation at the sites of elemental Strontium deposition. EPMA revealed uniform incorporation of Strontium over actively remodeling trabecular surfaces in normal control rats. That pattern was significantly altered after meniscectomy surgery resulting in greater Strontium signal at the developing osteophyte margins. Alendronate treatment inhibited osteophyte development by 40% and 51% quantified by micro-CT volumetric measurements at 4 and 8 weeks after surgery, respectively. Osteophytes in the alendronate group were more cartilaginous in composition [i.e., lower bone mineral density (BMD)] compared to the untreated group. Histological analysis confirmed the osteophyte inhibitory effect of alendronate, and also verified reduced degeneration of the articular cartilage compared to untreated rats. Our study confirmed that alendronate administration will reduce osteophyte formation in a rat model of post-traumatic osteoarthritis, partially through the inhibition of secondary remodeling of osteophytes. Our study is the first to employ elemental Strontium as a tracer of bone turnover in the pathogenesis of osteoarthritis and to assess the efficacy of bisphosphonate antiresorptive drug interventions on osteophytogenesis.
    Osteoarthritis and Cartilage 04/2012; 20(7):694-702. · 3.90 Impact Factor
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    Article: Trabecular reorganization in consecutive iliac crest biopsies when switching from bisphosphonate to strontium ranelate treatment.
    Björn Jobke, Andrew J Burghardt, Burkhard Muche, Michael Hahn, Jutta Semler, Michael Amling, Sharmila Majumdar, Björn Busse
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    ABSTRACT: Several agents are available to treat osteoporosis while addressing patient-specific medical needs. Individuals' residual risk to severe fracture may require changes in treatment strategy. Data at osseous cellular and microstructural levels due to a therapy switch between agents with different modes of action are rare. Our study on a series of five consecutively taken bone biopsies from an osteoporotic individual over a six-year period analyzes changes in cellular characteristics, bone microstructure and mineralization caused by a therapy switch from an antiresorptive (bisphosphonate) to a dual action bone agent (strontium ranelate). Biopsies were progressively taken from the iliac crest of a female patient. Four biopsies were taken during bisphosphonate therapy and one biopsy was taken after one year of strontium ranelate (SR) treatment. Furthermore, serum bone markers and dual x-ray absorptiometry measurements were acquired. Undecalcified histology was used to assess osteoid parameters and bone turnover. Structural indices and degree of mineralization were determined using microcomputed tomography, quantitative backscattered electron imaging, and combined energy dispersive x-ray/µ-x-ray-fluorescence microanalysis. Microstructural data revealed a notable increase in bone volume fraction after one year of SR treatment compared to the bisphosphonate treatment period. Indices of connectivity density, structure model index and trabecular bone pattern factor were predominantly enhanced indicating that the architectural transformation from trabecular rods to plates was responsible for the bone volume increase and less due to changes in trabecular thickness and number. Administration of SR following bisphosphonates led to a maintained mineralization profile with an uptake of strontium on the bone surface level. Reactivated osteoclasts designed tunneling, hook-like intratrabecular resorption sites. The appearance of tunneling resorption lacunae and the formation of both mini-modeling units and osteon-like structures within increased plate-like cancellous bone mass provides additional information on the mechanisms of strontium ranelate following bisphosphonate treatment, which may deserve special attention when monitoring a treatment switch.
    PLoS ONE 01/2011; 6(8):e23638. · 4.09 Impact Factor
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    Article: Bone mineralization: from tissue to crystal in normal and pathological contexts.
    Y Bala, D Farlay, G Boivin
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    ABSTRACT: Bone is a complex and structured material; its mechanical behavior results from an interaction between the properties of each level of its structural hierarchy. The degree of mineralization of bone (bone density measured at tissue level) and the characteristics of the mineral deposited (apatite crystals) are major determinants of bone strength. Bone remodeling activity acts as a regulator of the degree of mineralization and of the distribution of mineral at the tissue level, directly impacting bone mechanical properties. Recent findings have highlighted the need to understand the underlying process occurring at the nanostructure level that may be independent of bone remodeling itself. A more global comprehension of bone qualities will need further works designed to characterize what are the consequences on whole bone strength of changes at nano- or microstructure levels relative to each other.
    Osteoporosis International 12/2012; · 4.58 Impact Factor

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