Osteoporosis results from reduced bone mass and disruption of the micro-architecture of bone, giving decreased bone strength and increased risk of fracture, particularly of the spine, hip, wrist, humerus, and pelvis. Epidemiologically, fractures caused by osteoporosis affect one in two women and one in five men over the age of 50, resulting in an estimated annual cost to the health services of around 30 billion Euros in Europe with increased risk of disability and mortality [1,2].

Treatment of osteoporosis with strontium containing compounds was reported about 40 years ago [3,4]. Nowadays, a commercial strontium containing drug has been used clinically and shown to reduce vertebral and non-vertebral (including hip) fractures in postmenopausal women with osteoporosis [5,6]. The beneficial effects of strontium stem from the prevention of bone loss. In vitro studies showed that strontium ions (Sr²⁺) decreased the differentiation and resorping activity of osteoclasts as well as increased osteoclast apoptosis [7-9]. Meanwhile, Sr²⁺ was shown to enhance preosteoblastic cell proliferation and collagen synthesis [10]. Consequently, Sr²⁺ ions depress bone resorption and maintain bone formation.

Strontium-based and zinc-based ionomeric cements were tested for their osteoconductive properties [11] and the results indicated that ionomeric cement with higher Sr content was the most osteoconductive. Leroux et al. synthesized calcium strontium hydroxyapatites based on ionic calcium phosphate cements [12]. The presence of a significant amount of NO³⁻ containing impurities prevents its further application. Therefore, novel Sr-containing hydroxyapatite cement with no impurities in its final product was developed [13].

Substitution of calcium by strontium within amorphous calcium phosphate, apatitic calcium phosphate, hydroxyapatite, octacalcium phosphate and dicalcium phosphate dihydrate (DCPD) was studied [14]. It was reported that calcium substitution by strontium in DCPD was the most efficient, due to the fact that all Ca sites in the DCPD lattice can be occupied by Sr atoms [14].

Subsequently, brushite (DCPD) cement has the advantage of being resorbable [15], strontium substitution for calcium is more efficient [14] and the set brushite cement does not have harmful impurities [15]. For this reason, brushite cement set with 1M glycolic acid was modified by the addition of 1%, 2%, 5%, 8%, and 10% (w/w) SrCl₂. Thereafter, the effect of the added SrCl₂ on cement microstructure, final setting time, cohesion, diameter tensile strength and morphology was studied.

The effect of SrCl₂ on the cement setting reaction was concentration dependent as indicated by the measurement of the cement FST. Such that the addition of low concentration of SrCl₂ did not significantly affect the cement FST, whereas concentrations of 5% and 10% (w/w) SrCl₂ increased the cement FST to ca. 20 and 45 minutes, respectively (Table 1). Moreover, it was observed that the cement paste was more liquid-like with the increase in SrCl₂ concentration.

The presence of Sr²⁺ in the cement paste seems to affect the cement diameter tensile strength. Unmodified brushite cement had a diameter tensile strength of 3.2 ± 0.7 MPa. SrCl₂ concentrations up to 5% did not significantly affect the cement tensile strength. Nevertheless, the addition of 10% (w/w) SrCl₂ decreased the cement tensile strength to ca. 2 MPa (Figure 1).

Herein, the cement solid weight loss was used as an indicator for cement cohesion as reported in previous studies [17-19]. The cement weight loss was generally increased with the increase in SrCl₂ concentration (Figure 2). The solid weight loss of Sr-free cements was about 0.5% that was increased to ca. 0.9 and 1.7% for cements prepared with SrCl₂ of 5 and 10%. The released particles were β-TCP as indicated by FTIR spectroscopy (Figure 3).

Rietveld analysis of the XRD spectra of cement samples was summarized in Table 2. The cement matrix were composed of β-TCP in a predominantly brushite matrix (Figure 4). The diffraction peaks of brushite are shifted toward lower diffraction angles indicating an increase in unit cell volume. The relative amount of brushite in cement matrix did not seem to be affected by the increase in SrCl₂. Rietveld refinement of brushite unit cell parameters indicated a conspicuous increase in the parameters value with the increase in strontium concentration up to 8% (w/w). However, the unit cell parameters a, c decreased while the b increased at 10% (w/w) SrCl₂ (Table 2). Nevertheless, the unit cell volume calculated for monoclinic system increased linearly for all SrCl₂ concentrations (Figure 5).

The unit cell of DCPD contains four calcium and four phosphorus atoms. The Ca and P atoms are linked to form corrugated sheets where each two sheets are joined together by water molecules. All Ca sites in the crystal lattice are characterized by almost identical coordination [14]. As all Ca sites in the DCPD lattice can be occupied by Sr atoms, brushite cements could be used as a delivery system for strontium ions.

Strontium ions were successfully incorporated in the structure of brushite crystals as evidenced by an increase of unit cell volume with the increased strontium content (Figure 5). This is related to the fact that the ionic radius of Sr²⁺ (1.13 Å) is larger than calcium ion (1.00 Å).

Brushite cement FST was increased significantly at high SrCl₂ concentration (Table 1). The dissolution of the basic β-TCP is determinant to brushite cement FST. Christoffersen et al. reported that Sr²⁺ inhibits the rate of dissolution of hydroxyapatite, similarly, the presence of Sr²⁺ in the cement paste could inhibit the dissolution rate of β-TCP increasing the cement FST [20]. Strontium ions were also reported to inhibit apatite deposition and retard calcium phosphate precipitation. Thus, Sr²⁺ could inhibit brushite crystal growth [21] and increase the cement FST.

The solid particles released from the brushite cements were β-TCP. Cement solid weight loss was used to indicate brushite cement cohesion [17-19]. Brushite solubility affects the cement cohesion as reported in a previous study [17); such that the more soluble the brushite crystals are, the more β-TCP particles are released. It was reported that strontium substitution for calcium expands hydroxyapatite crystals lattice and increases their solubility [20]. Herein, strontium incorporation causes brushite crystals to expand and thus decreases their stability, resulting in more soluble brushite crystals. Consequently, β-TCP particles release and cement solid weight loss increased.

Brushite cement diameter tensile strength was significantly affected when 10% (w/w) SrCl₂ was added. At this concentration, strontium content within brushite lattice was the highest as indicated by cell unit volume. This high content of strontium may decrease the microhardness of brushite crystals and, therefore, the cement diameter tensile strength. Cement porosity is determinant to the cement mechanical properties. The increased solubility of Sr-containing brushite crystals could increase the number and/or the size of cement pores and thus decrease cement tensile strength.

The modification of brushite cements with strontium chloride is efficient to induce calcium ions substitution by strontium ions.