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. First described by Brown and Chow in 1983 and brought to clinical use as the Skeletal Repair System (Norian SRS) in the 1990s, they fill the gap between inert acrylic cement (PMMA) and biological graft. They are osteoconductive but not osteoinductive or osteogenic, set at body temperature by a dissolution–precipitation (isothermic) reaction with no toxic monomer, develop high compressive but very low tensile/shear strength, and are gradually resorbed and replaced by host bone (osteotransduction). Their niche is the contained metaphyseal void — buttressing an elevated articular fragment against subsidence while internal fixation neutralises bending and shear.

The four properties that define any bone-graft substitute

• Osteoconduction — passive scaffold for ingrowth. CPC has this.
• Osteoinduction — signalling (BMPs) that recruits/differentiates osteoprogenitors. CPC lacks this.
• Osteogenesis — living transplanted cells. CPC lacks this.
• Structural support — immediate mechanical load-sharing. CPC provides this in compression only.

Why CPC works as a strut, not a plate CPC behaves like a ceramic: strong when squeezed (20-50 MPa, exceeding cancellous bone) but brittle and weak in tension/shear (2-5 MPa). It therefore supports a subarticular fragment against axial collapse but will fracture under bending — so it is always combined with neutralising/buttress hardware, never used alone in a load-bearing site.

Composition

Powder Components

• Tetracalcium phosphate (TTCP): Ca₄(PO₄)₂O
• Dicalcium phosphate anhydrous (DCPA): CaHPO₄
• α-Tricalcium phosphate (α-TCP): α-Ca₃(PO₄)₂
• Calcium carbonate, calcium oxide (modifiers)

Liquid Phase

• Water or sodium phosphate solution
• pH modifiers
• Accelerators (e.g., citric acid)

Setting Reaction

Mechanism

1. Powder dissolves in liquid (acidic microenvironment)
2. Supersaturation of calcium and phosphate ions
3. Precipitation of new crystalline phase
4. Interlocking crystal network provides mechanical strength

Key Characteristics

• Isothermic: No heat generated (unlike PMMA)
• Time: 10-30 minutes working time, 24 hours for full strength
• Environment: Sets in aqueous (wet) environment

Microstructure

Porosity

• Macropores (100-500 μm): Created by incorporation techniques
• Micropores (1-10 μm): Inherent to setting reaction
• High surface area enhances osteoconduction

Crystal Structure

• Hydroxyapatite: Hexagonal crystals
• Brushite: Monoclinic crystals
• Similar to biological bone mineral

The topic invokes "osteotransduction" repeatedly and the controversies note that "rapid resorption may outpace bone formation", but the mechanism that makes a calcium phosphate cement different from an inert filler is never spelled out. It is the single concept that separates CaP from PMMA.

Osteotransduction = creeping substitution. Unlike PMMA (which is simply encapsulated and stays forever), a CaP cement is biologically turned over and replaced by host bone. The process couples two activities 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.

Why the rate must match. The clinical performance of a cement depends on whether resorption and bone formation stay in step:

Resorption rate is tunable through chemistry and structure - higher porosity and surface area, smaller crystals and the brushite (vs apatite) 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.

Primary Indications

Metaphyseal Fractures

• Tibial plateau: Schatzker II, III, VI with articular depression
• Distal radius: Metaphyseal void after reduction in osteoporotic bone
• Calcaneal fractures: Structural support of posterior facet
• Proximal humerus: Metaphyseal void filling

Tumour Surgery

• Curettage of benign bone tumours (GCT, ABC, unicameral bone cyst)
• Filling defect after tumour removal
• May be combined with autograft/allograft

Vertebral Augmentation

• Alternative to PMMA for kyphoplasty/vertebroplasty
• Lower exothermic risk but higher cost

Contraindications

Absolute

• Active infection
• Uncontained defects (cement will leak)
• Load-bearing diaphyseal sites

Relative

• Large defects requiring structural support
• Poor soft tissue coverage
• Immunocompromised patients

The Larsson review, the controversies section and an explicit viva follow-up ("how does cement augmentation improve screw pull-out in osteoporotic bone?") all invoke cement augmentation of metalwork, yet the concept is never developed. It 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 and pull-out and cut-out are the dominant failure modes - the metalwork is fine, the bone holds it poorly.

How cement augmentation works. Injecting a small volume of cement around the screw tip (often through a cannulated/fenestrated screw) before final tightening:

• Increases the effective bone-implant interface - the cured cement interdigitates with surrounding trabeculae and converts a few thread-bone contacts into a large, load-distributing cement-bone block;
• Spreads load over a wider volume, lowering the peak stress at any single trabecula and resisting the toggling that causes cut-out;
• Raises pull-out force, stiffness and fatigue life of the construct - cadaveric work (Larsson & 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 versus PMMA for augmentation. Both are used; the trade-off mirrors the void-filling story:

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. A permanent PMMA mass in particular can complicate any future revision.

Compressive Strength

Tensile/Shear Strength

• CaP Cement: 2-5 MPa (very low)
• PMMA: 25-40 MPa
• Cortical Bone: 50-150 MPa

Clinical Implication: CaP cements are brittle; require hardware protection (plate, screws) in fracture treatment

Modulus of Elasticity

• CaP cements: 5-15 GPa
• Cancellous bone: 0.1-1 GPa
• Cortical bone: 15-20 GPa

Fatigue Properties

• Limited fatigue resistance
• Catastrophic failure under cyclic loading
• Not suitable for high-stress cyclical loading

By End Product

By Form

Injectable

• Paste form, delivered via syringe
• Sets in situ after injection
• Ideal for minimally invasive application
• Examples: Norian SRS, HydroSet

Pre-formed

• Blocks, granules, or putty
• Shaped before or during surgery
• Higher initial strength

By Application

Commercial Products

• Norian SRS/CRS: Apatite cement, high strength
• ChronOS: β-TCP based, resorbable
• α-BSM: Injectable, fast-setting
• HydroSet: Brushite based, faster resorption

When a metaphyseal or cavitary defect must be filled, the realistic options are compared below. The "diagnosis" the examiner wants is matching the right filler to the defect (containment, load, biology needed).

Algorithm

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Immediate

Weight-Bearing

• Protected weight-bearing initially
• Progressive loading as bone heals
• Hardware provides protection during healing

Monitoring

• Standard wound care
• Watch for signs of extravasation
• Imaging at 2 and 6 weeks

Medium-Term

Rehabilitation

• Range of motion as tolerated
• Strengthening when fracture stable
• Progress based on clinical and radiographic healing

Imaging Follow-up

• X-rays at 6, 12 weeks
• Assess fracture healing and cement integration
• CT if concern about resorption

Long-Term

Cement Remodeling

• Brushite: 6-12 months
• Apatite: Years to decades
• Gradual replacement by host bone

Hardware Removal

• Consider once fracture healed
• Cement usually incorporated or resorbed
• Not routinely required

Material-Related

Cement Extravasation

• Leakage into soft tissues or joint
• More common with uncontained defects
• Usually resorbs without issue (unlike PMMA)

Incomplete Fill

• Air pockets reduce strength
• May require reoperation
• Prevented by proper technique

Brittleness/Fracture

• Catastrophic failure under shear
• Requires hardware protection
• More common in brushite cements

Clinical Complications

Infection

• Not inherent to material
• Biofilm formation possible
• Requires debridement if occurs

Delayed Resorption

• Apatite cements may persist for years
• Usually asymptomatic
• May interfere with future surgery

Subsidence

• Despite cement support
• Usually due to poor technique or osteoporosis
• Hardware failure common cause

Comparison to Alternatives

Clinical Outcomes

Tibial Plateau Fractures

• Reduced articular subsidence vs autograft
• Equivalent functional outcomes
• No donor site morbidity

Distal Radius Fractures

• Maintains reduction in osteoporotic bone
• Faster return to function
• Equivalent long-term outcomes

Radiographic Outcomes

Cement Incorporation

• Evidence of bone ingrowth at 6-12 months
• Progressive replacement by host bone
• Apatite cements may remain visible longer

Subsidence Prevention

• Superior to autograft for structural support
• 2-3 mm less subsidence in tibial plateau studies
• Maintains articular congruity

Functional Outcomes

Patient-Reported Outcomes

• No difference in pain scores
• Equivalent range of motion
• No donor site morbidity (vs autograft)

Return to Activity

• Similar timeframes to other grafts
• Hardware removal rates similar
• Long-term function maintained

Pre-operative Planning

Patient Selection

• Contained metaphyseal defect
• Adequate soft tissue coverage
• No active infection

Defect Assessment

• Size and containment
• Load-bearing requirements
• Need for structural vs void-filling

Intraoperative Considerations

Preparation

• Read manufacturer instructions carefully
• Ensure powder/liquid ratio correct
• Prepare before need (limited working time)

Working Time

• Typically 10-15 minutes
• Temperature affects setting (faster if warm)
• Must be injected before setting begins

Adjuncts

Hardware Protection

• Buttress plating for metaphyseal fractures
• Prevents shear/tensile failure
• Essential for weight-bearing bones

Combination with Biologics

• May add autograft for osteoinduction
• Platelet-rich plasma (theoretical benefit)
• BMP addition (research stage)

Tibial Plateau Example

Step 1: Fracture Reduction

• Elevate depressed articular segment
• Use bone tamp or elevator through cortical window
• Confirm reduction under fluoroscopy

Step 2: Cement Preparation

• Mix powder and liquid per manufacturer
• Achieve paste consistency
• Work within time window

Step 3: Cement Application

• Inject through cortical window or cannula
• Fill void completely (no air pockets)
• Overfill slightly (will compress)

Step 4: Hardware Application

• Apply buttress plate before cement sets
• Screws through or around cement
• Provides protection against shear forces

Step 5: Confirmation

• Fluoroscopy to confirm fill and reduction
• Check cement containment
• Assess hardware position

Key Technical Points

Containment

• Create cortical window if needed
• Block significant egress points
• May use small bone graft to contain

Bleeding Control

• Lavage defect before injection
• Blood dilutes cement, weakens setting
• Tourniquet useful if applicable

Setting Confirmation

• Wait for initial set before wound closure
• Typically 15-30 minutes
• Test with probe

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.

Calcium phosphate cements are synthetic bone void fillers that mimic the mineral phase of bone (hydroxyapatite) and are osteoconductive but not osteoinductive. They set via an isothermic (non-exothermic) precipitation reaction, unlike PMMA which generates thermal necrosis risk. Key properties include high compressive strength (20-50 MPa, greater than cancellous bone) but low tensile/shear strength, making hardware protection essential. Primary applications include metaphyseal void filling in tibial plateau fractures and distal radius fractures, where they prevent articular subsidence. Over 6-18 months, osteoclasts remodel the cement and replace it with host bone through osteotransduction.

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.