Calcium Phosphate Cements

Calcium phosphate cements (CPCs) are synthetic, injectable bone-void fillers whose set product is the same mineral phase as bone, carbonated apatite or brushite. Brown and Chow first described them in 1983, and they reached clinical use in the 1990s as the Skeletal Repair System (Norian SRS). They fill the gap between inert acrylic cement (PMMA) and biological graft.

What they do. A CPC sets at body temperature by a dissolution-precipitation reaction that is isothermic and releases no toxic monomer. The set cement has high compressive but very low tensile and shear strength, and it is gradually resorbed and replaced by host bone, a process called osteotransduction.

Where they belong. The niche is the contained metaphyseal void: the cement buttresses an elevated articular fragment against subsidence while internal fixation neutralises bending and shear. Primary applications include metaphyseal void filling in tibial plateau and distal radius fractures.

Any bone-graft substitute is judged on four properties, and a CPC has only two of them:

• Osteoconduction - a passive scaffold for ingrowth. CPC has it, as do allograft and autograft
• Osteoinduction - signalling (BMPs) that recruits and differentiates osteoprogenitors. CPC lacks it; BMP-2, autograft and DBM provide it
• Osteogenesis - living transplanted cells. CPC lacks it; autograft and RIA provide it
• Structural support - immediate mechanical load-sharing. CPC provides it in compression only

Composition. The cement is mixed from a powder and a liquid phase.

• Powder - tetracalcium phosphate (TTCP, Ca₄(PO₄)₂O), dicalcium phosphate anhydrous (DCPA, CaHPO₄) and α-tricalcium phosphate (α-TCP, α-Ca₃(PO₄)₂), with calcium carbonate and calcium oxide as modifiers
• Liquid - water or sodium phosphate solution, with pH modifiers and accelerators such as citric acid

The setting reaction. Mixing starts a dissolution-precipitation sequence:

1. The powder dissolves in the liquid, in an acidic microenvironment
2. Calcium and phosphate ions reach supersaturation
3. A new crystalline phase precipitates
4. The interlocking crystal network provides the mechanical strength

The reaction generates no heat, unlike PMMA, and it sets in an aqueous (wet) environment. The cement sets over 10-30 minutes and reaches full strength at 24 hours.

Microstructure. Micropores of 1-10 μm are inherent to the setting reaction; macropores of 100-500 μm are created by incorporation techniques. The high surface area enhances osteoconduction. Hydroxyapatite forms hexagonal crystals and brushite monoclinic ones, and both are similar to biological bone mineral.

Metaphyseal fractures. The cement fills or supports the metaphyseal void at four sites:

• Tibial plateau - Schatzker II, III and VI with articular depression
• Distal radius - metaphyseal void after reduction in elderly osteoporotic bone
• Calcaneus - structural support of the posterior facet
• Proximal humerus - metaphyseal void filling

The tibial plateau. Once the depressed articular surface is elevated, the cement fills the metaphyseal void beneath it. Unlike cancellous chips, it gives immediate structural support against re-collapse and subsidence before the plate takes full load.

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Tumour surgery. After curettage of a benign bone tumour (GCT, ABC, unicameral bone cyst) the cement fills the defect, and it may be combined with autograft or allograft.

Vertebral augmentation. CaP cement is an alternative to PMMA for kyphoplasty and vertebroplasty, with lower exothermic risk but higher cost.

Contraindications. They are graded as absolute or relative:

• Absolute - active infection; an uncontained defect, from which the cement will leak; a load-bearing diaphyseal site
• Relative - a large defect requiring structural support; poor soft-tissue coverage; an immunocompromised patient

Augmenting metalwork is the second major use of CaP cement beyond void filling, and a recurring exam question in osteoporotic fixation.

The problem. In osteoporotic bone the trabeculae are sparse, so a screw thread engages little bone. Pull-out and cut-out are the dominant failure modes: the metalwork is fine, the bone holds it poorly.

How augmentation works. A small volume of cement is injected around the screw tip, often through a cannulated or fenestrated screw, before final tightening. The cured cement interdigitates with the surrounding trabeculae and converts a few thread-bone contacts into a large, load-distributing cement-bone block. Spreading the load over a wider volume lowers the peak stress at any single trabecula and resists the toggling that causes cut-out.

What it buys. Pull-out force, stiffness and fatigue life of the construct all rise. Cadaveric work (Larsson and Bauer) consistently shows cement-augmented metal fixation is stiffer and stronger than metal alone in the distal radius, tibial plateau, proximal femur and calcaneus.

CaP or PMMA. Both are used, and the trade-off mirrors the void-filling story. Prefer CaP when later remodelling and easier revision are wanted; PMMA is tougher, but a permanent PMMA mass can complicate any future revision.

The caveats. Augmentation is an adjunct that buys early fixation in poor bone; it does not correct malreduction. The evidence is largely biomechanical (cadaveric) rather than high-level clinical, and leakage into a joint or fracture gap must be avoided.

Planning. Assess the defect's size and containment, the load it must bear, and whether it needs structural support or simply a void filled.

Preparation. Read the manufacturer's instructions carefully, get the powder-to-liquid ratio right and prepare the cement before it is needed. Working time is typically 10-15 minutes, setting is faster if warm, and the cement must be injected before setting begins.

The tibial plateau, step by step.

1. Reduce - elevate the depressed articular segment with a bone tamp or elevator through a cortical window, and confirm the reduction under fluoroscopy
2. Prepare - mix powder and liquid per the manufacturer to a paste consistency, working within the time window
3. Inject - through the cortical window or a cannula, filling the void completely with no air pockets, and overfill slightly because it will compress
4. Fix - apply the buttress plate before the cement sets, with screws through or around the cement, to protect against shear forces
5. Confirm - check fill, reduction, cement containment and hardware position under fluoroscopy

Containment. Create a cortical window if needed and block significant egress points; a small bone graft may be used to contain the cement.

Bleeding. Blood dilutes the cement and weakens its setting, so lavage the defect before injection. A tourniquet is useful where applicable.

Setting. Wait for the initial set before wound closure, typically 15-30 minutes, and test it with a probe.

Adjuncts. Buttress plating of metaphyseal fractures prevents shear and tensile failure and is essential in weight-bearing bones. Autograft may be added for osteoinduction; platelet-rich plasma has a theoretical benefit, and BMP addition is at the research stage.

By end product. The two end products differ in stoichiometry, in how fast they are resorbed and in strength (the figures are under Mechanical Properties).

By form. Injectable cements are pastes delivered by syringe that set in situ after injection, which suits minimally invasive application; Norian SRS and HydroSet are examples. Pre-formed cements come as blocks, granules or putty, are shaped before or during surgery, and have higher initial strength.

By application. The product is chosen for the property the site needs:

Commercial products. Each name maps to a phase or a handling property:

• Norian SRS/CRS - apatite cement, high strength
• ChronOS - β-TCP based, resorbable
• α-BSM - injectable, fast-setting
• HydroSet - brushite based, faster resorption

A strut, not a plate. CPC behaves like a ceramic: strong when squeezed, brittle and weak in tension and shear. It supports a subarticular fragment against axial collapse but will fracture under bending, so it is always combined with neutralising or buttress hardware and never used alone in a load-bearing site.

Compression. In compression the cement is stronger than cancellous bone, which is what lets it prevent subsidence.

Tension and shear. Here the cement is very weak, 2-5 MPa, against 25-40 MPa for PMMA and 50-150 MPa for cortical bone.

Stiffness. The modulus of elasticity of CaP cement is 5-15 GPa, against 0.1-1 GPa for cancellous bone and 15-20 GPa for cortical bone.

Fatigue. Fatigue resistance is limited and failure under cyclic loading is catastrophic, so the cement is not suitable for high-stress cyclical loading.

Creeping substitution. PMMA is simply encapsulated and stays forever; a CaP cement is biologically turned over and replaced by host bone. Two activities are coupled at the cement surface:

• Cell-mediated resorption - osteoclasts (and giant cells) resorb the cement much as they resorb bone, supplemented by simple chemical dissolution
• Appositional bone formation - osteoblasts lay down new bone onto the osteoconductive cement surface as it is resorbed

The result is gradual, front-by-front replacement of cement by living bone, the same creeping substitution seen with structural allograft.

The rates must match. How a cement performs clinically depends on whether resorption and bone formation stay in step. That balance, not raw strength, is what makes a good cement.

Tuning the rate. Resorption is tunable through chemistry and structure: higher porosity and surface area, smaller crystals and the brushite phase all resorb faster. Brushite is designed for speed but can paradoxically convert to poorly resorbing apatite in vivo, which is why the ideal match remains unsolved.

When a metaphyseal or cavitary defect must be filled, the answer the examiner wants is the right filler for the defect: its containment, the load it must carry and the biology it needs.

Against PMMA and calcium sulfate. Calcium sulfate belongs in the comparison because it is the material calcium phosphate is most often confused with.

Calcium sulfate is a question of timing. It dissolves chemically over roughly six to twelve weeks, frequently faster than bone can fill the space. It can therefore leave a radiolucent void that is mistaken for infection or non-union, and its dissolution products draw fluid, producing the sterile serous wound drainage that is its characteristic complication.

Apatite is slower than most texts imply. It is removed cell by cell by osteoclasts over years, which is why residual cement on a two-year radiograph is expected rather than a failure.

Match the material to the question. A defect that needs structural support until union takes calcium phosphate. A defect being filled as an antibiotic carrier, or as a simple space-holder in a well-supported location, can take calcium sulfate.

Extravasation. Cement can leak into the soft tissues or joint, more commonly from an uncontained defect. It usually resorbs without issue, unlike PMMA.

Incomplete fill. Air pockets reduce strength and may require reoperation; proper technique prevents them.

Cement fracture. Failure under shear is catastrophic, and more common in brushite cements.

Infection. Infection is not inherent to the material, but biofilm formation is possible, and it requires debridement if it occurs. The infection risk is low with CaP cement, PMMA and autograft alike.

Subsidence. Subsidence can occur despite cement support, usually from poor technique or osteoporosis, and hardware failure is a common cause.

Weight-bearing. Protected weight-bearing at first, progressing as the bone heals; the hardware provides protection during healing.

Monitoring. Standard wound care, watching for signs of extravasation. Imaging at 2, 6 and 12 weeks assesses fracture healing and cement integration, with CT if there is concern about resorption.

Rehabilitation. Range of motion as tolerated, strengthening once the fracture is stable, and progression guided by clinical and radiographic healing.

Hardware removal. Not routinely required; consider it once the fracture has healed. The cement is usually incorporated or resorbed.

Tibial plateau. Cement is superior to autograft for structural support: less articular subsidence, 2-3 mm less in tibial plateau studies, maintained articular congruity and no donor-site morbidity. Functional outcomes have been reported as equivalent, but the landmark trial below reported no validated functional or patient-reported outcome; its single significant result is radiographic.

Distal radius. Cement is reported to maintain reduction in osteoporotic bone, with faster return to function and equivalent long-term outcomes. The Cassidy trial in the Evidence Base qualifies the first claim: ulnar variance collapsed more in the cement group, and extraosseous cement carried the highest loss of reduction.

Incorporation. Bone ingrowth is evident at 6-12 months, followed by progressive replacement by host bone; apatite cements may remain visible longer.

Patient-reported outcomes. There is no difference in pain scores and range of motion is equivalent, without the donor-site morbidity of autograft. Return to activity follows similar timeframes to other grafts, hardware removal rates are similar and long-term function is maintained. The one pain benefit in the evidence below, from the Bajammal meta-analysis, is against no graft at all.

Global Epidemiology & Use

• Bone-graft substitutes are used in a large minority of fracture and reconstructive procedures worldwide; CaP cements are the dominant injectable, resorbable, structural option for contained metaphyseal voids.
• Highest-volume indications globally: tibial plateau, distal radius (osteoporotic), calcaneus and proximal humerus metaphyseal voids, and curettage cavities after benign bone lesions.
• Uptake tracks with availability of fluoroscopy, theatre cost tolerance and surgeon familiarity rather than any single national guideline.

Society Guidance, Side by Side

No major society endorses CaP cement as a stand-alone load-bearing construct; all frame it as an adjunct to internal fixation.

Regulatory & Registry Notes

• Regulated as implantable medical devices (e.g. FDA in the US, CE-mark/MDR in Europe). Norian SRS holds long-standing approval for selected distal radius and other metaphyseal fractures.
• There is no dedicated international registry for bone-graft substitutes comparable to arthroplasty registries (NJR, AJRR, AOANJRR); evidence rests on RCTs and meta-analysis (Bajammal 2008; Russell & Leighton 2008; Cassidy 2003) rather than registry survival data.

High- vs Limited-Resource Practice

• Well-resourced settings: ready access to injectable apatite/brushite cements and intra-operative imaging; cement chosen to avoid iliac-crest harvest morbidity.
• Limited-resource settings: autograft (iliac crest, RIA) and allograft remain first-line because synthetic cement cost and supply are limiting; the structural advantage of cement is weighed against expense.

• Apatite vs brushite resorption. Brushite is designed to resorb faster, but in vivo it can convert to poorly-resorbing apatite, and rapid resorption may outpace bone formation — leaving a transient defect. The "ideal" resorption-to-formation match is not solved.
• Extraosseous extravasation. In the distal radius RCT (Cassidy 2003), cement was extraosseous in 70% of wrists and that subgroup had the highest loss of reduction — the clinical significance of leakage versus a marker of poor containment is debated.
• Does it accelerate union or just resist subsidence? Trials consistently show better maintenance of reduction, but a true acceleration of fracture healing is not established; benefit may be purely mechanical.
• Stand-alone augmentation in osteoporotic fixation. Screw-tip cement augmentation improves pull-out in cadaver studies, but high-quality clinical evidence for routine use (and concern over complicating revision) remains limited.
• Vertebroplasty/kyphoplasty. CaP avoids PMMA's exotherm and monomer but has lower fatigue strength and higher cost; whether it improves outcomes over PMMA in the spine is unresolved.
• Function vs radiographs. Several RCTs show radiographic superiority (less subsidence) without a durable difference in patient-reported function at one year — the patient-relevant value is questioned.

1. Larsson S, Bauer TW. Use of injectable calcium phosphate cements for fracture fixation: a review. Clin Orthop Relat Res. 2002.
2. Bajammal SS, et al. The use of calcium phosphate bone cement in fracture treatment. JBJS Am. 2008.