Strontium incorporates at sites critical for bone mineralization in rats with renal failure

Abstract

We previously demonstrated the development of a mineralization defect during strontium administration and its reversibility after withdrawal in rats with chronic renal failure. Recently, strontium ranelate has been introduced as a therapeutic agent for osteoporosis. However, caution has to be taken, as this bone disorder mainly develops in elderly people who may present a moderately decreased renal function. In order to assess the ultra-structural localization of strontium in bone and thereby to get a better insight into the element's systemic effects on bone, synchrotron-based x-ray micro-fluorescence was applied, which showed that after 2 weeks of strontium loading (2 g l −1 in drinking water) in rats with renal failure, concomitant with the development of impaired mineralization, the element was localized mainly at the outer edge of the mineralized bone, while after longer loading periods, a more homogeneous distribution was found. After washout, strontium was found at sites deeper within the trabeculae, while newly deposited low-strontium-containing mineral was found at the outer edges. Synchrotron x-ray microdiffraction analysis showed that strontium is incorporated in the apatite crystal lattice through exchange with calcium.The results show that strontium is initially incorporated in bone at sites of active bone mineralization, close to the osteoid/mineralization front. Most likely, strontium binds to matrix proteins serving as crystal nucleation points and by heteroionic substitution with calcium within the hydroxyapatite crystals, thereby impairing further hydroxyapatite formation. After withdrawal, strontium is released from these sites, by which mineralization is restored and the previously formed strontium-containing hydroxyapatite is buried under a new layer of mineralized bone.

Bone integration capability of a series of strontium‐containing hydroxyapatite coatings formed by micro‐arc oxidation

“…[14][15][16] Our study reveals the potential of 20%Sr-HA coatings in dental and orthopedic applications. Thus, local application of strontium may be an alternative method to enhance implant osseointegration and to avoid the potential adverse reactions induced by systemic administered strontium.…”

“…[5][6][7][8][9] Evidence from in vitro data has proved that Sr favors bone healing via a unique mechanism by reducing bone resorption while promoting bone formation, 10,11 where Sr has been shown to enhance preosteoblasts proliferation and bone collagen synthesis as well as decrease bone resorption by inhibiting the osteoclast resorbing activity and osteoclastic differentiation. [14][15][16] The uptake of strontium has been shown to be dose-dependent, which distribution mainly in newly formed compact and cancellous bone. 12 Therefore, Sr salt has been put forward as a therapeutic agent to improve implant osseointegration in vivo.…”

“…11 The dual action of Sr 11 results in a rebalance in bone turnover and improves bone microarchitecture and strength. 16 Animal studies demonstrate that high doses of strontium induce alterations of mineralization and even cause the development of osteomalacia in a rat model with chronic renal failure. 13 Nevertheless, studies have demonstrated an association between the accumulation of strontium in bone and the presence of osteomalacia.…”

“…13 Nevertheless, studies have demonstrated an association between the accumulation of strontium in bone and the presence of osteomalacia. [14][15][16] The uptake of strontium has been shown to be dose-dependent, which distribution mainly in newly formed compact and cancellous bone. 16 Animal studies demonstrate that high doses of strontium induce alterations of mineralization and even cause the development of osteomalacia in a rat model with chronic renal failure.…”

“…[14][15][16] The uptake of strontium has been shown to be dose-dependent, which distribution mainly in newly formed compact and cancellous bone. 16 Animal studies demonstrate that high doses of strontium induce alterations of mineralization and even cause the development of osteomalacia in a rat model with chronic renal failure. 14 As the target population for strontium treatment consists mainly of elderly osteoporotic patients, who may have a reduced renal function, the increased risk for accumulation of the element should be considered.…”