Ann Thorac Surg 2009;88:1658-1661. doi:10.1016/j.athoracsur.2009.05.058
© 2009 The Society of Thoracic Surgeons
New Technology
Calcium Phosphate Cements Improve Bone Density When Used in Osteoporotic Sternums
Derek D. Muehrcke, MD, FACSa,*,
Will M. Shimp, PA-Ca,
Rafael Aponte-Lopez, MDb
a Department of Cardiac Surgery, Flagler Hospital, St. Augustine, Florida
b Department of Radiology, Flagler Hospital, St. Augustine, Florida
Accepted for publication May 15, 2009.
* Address correspondence to Dr Muehrcke, 300 Health Park Blvd, Suite 5000, St. Augustine, FL 32086 (Email: dmuehrcke{at}aol.com).
 |
Abstract
|
|---|
Purpose: Calcium phosphate cements control bleeding and are safe to use in osteoporotic sternums during open heart surgery. We looked at the clinical and radiographic effects of this agent on bone healing.
Description: Since March 2006, 18 patients had calcium phosphate cement inserted in their sternal tables at heart surgery. They were followed-up by office visits and chest computed tomographic (CT) scans. All preoperative and postoperative CT chest scans were evaluated for cement absorption, bone replacement, and bone density.
Evaluation: Five preoperative and 41 postoperative CT chest scans were available for evaluation. Median interval from surgery to CT scan was 531 days (range, 3 to 966 days). At follow-up there were neither clinical dehiscences nor nonunions of the sternums. Calcium phosphate cement appears to reabsorb quickly, but not completely. Five patients with pre-surgical CT chest scans demonstrated an average, improved bone density of 281.66 Hounsfield units at follow-up (p = 0.006).
Conclusions: In each patient, cement was replaced by new bone, and there is evidence that more bone is present as a result of cement use.
|
Introduction
|
|---|
We previously reported the successful use of calcium phosphate cements as a hemostatic agent in osteoporotic patients with large sternal marrow defects after cardiac surgery [1]. In our original study, 11 patients had no adverse reactions to the hydroxyapatite cement, and none required re-exploration for bleeding. A limited subset of patients demonstrated early bone replacement of the cement on computed tomographic (CT) scan. We used calcium phosphate cements to avoid copious amounts of bone wax and its inherent complications [2]. We have followed these patients and others to evaluate the radiologic and clinical intermediate-term results of sternal healing using these cements.
|
Technology
|
|---|
Eighteen patients undergoing open heart surgery through a median sternotomy incision between March 2006 and July 2008 were treated with the calcium phosphate cement Callos (Skeletal Kinetics, Cupertino, CA) to control persistent bleeding from their severely osteoporotic sternum after open heart surgery. Each had a large sternal bone marrow defect due to osteoporosis that involved at least 35% of their sternal surface between the sternal tables and was 1-cm deep (Fig 1). Only patients with extremely friable osteoporotic sternums received the study product. The decision to use Callos (Skeletal Kinetics) was made at the end of surgery to primarily stop sternal table bleeding.
|
Technique
|
|---|
Typically, 5 cc of cement filler was used per patient in an effort to avoid using bone wax. The product was applied with a thick paper spatula and digitally to fill all the defects between the sternal tables in a fashion similar to placing caulk between tiles (Fig 2). The cement was used as bone void filler, as well as to control bleeding. The sternal halves were packed full to capacity in an effort to tamponade sternal bleeding. No other topical hemostatic agents were used. Standard cardiopulmonary bypass techniques were used. Seventeen patients underwent coronary artery bypass grafting and 5 had one or more valves repaired or replaced. Patient characteristics are shown in Table 1. None of these patients were on bone replacement medicines.
Each sternum was closed with eight sternal wires and was irrigated with an antibiotic solution before placement of the cement. No other mechanical methods were used to stabilize the sternum. Hospital institutional review board sanction was obtained (August 8, 2008), and consents for the study were obtained on all subjects included in the study.
Patients were followed-up with office visits and CT scans (all patients). Scans were reviewed by one radiologist (RA-L) for the presence of retained calcium phosphate cement, bone healing, replacement of cement with bone over time, evidence of osteomyelitis, nonunion of the sternum, quantification of continual calcium phosphate cement in the sternum, and new bone density. New bone density was determined by comparing bone window image Hounsfield units in patients with preoperative chest CT scans to their respective postoperative scans at the same sternal level. Bone density was compared between postoperative scans in the same patient, if multiple postoperative scans were available.
All patients were seen in the office after surgery in follow-up. In 16 patients high-resolution CT chest scans were obtained at the time of follow-up (GE Lightspeed, QX/I, 4-slice scanner, software version 07MW11.10; General Electric Corp, Milwaukee, WI). Retrospective reconstructions were performed using a lung algorithm with retrospective slices at 1.25-mm thickness (detector configuration, 4 x 1.25) with 0.6-mm spacing (50% overlap) to reconstruct. Reformatted coronal images were made at 1.25-mm spacing.
|
Clinical Experience
|
|---|
Forty-one postoperative scans were performed in the 18 patients during the study period. Five patients had preoperative CT chest scans. Twelve patents had multiple scans for review (ie, two to seven postoperative scans). The shortest interval between scans was 6 days and the longest was 686 days. The median time between surgery and CT scanning was 531 days (range, 3 to 966 days).
No patient suffered clinical dehiscence or nonunion. No patients suffered sternal wound infections. One patient died at 201 days after surgery of chronic obstructive lung disease. Eleven patients had CT scans far enough apart to evaluate the rate of new bone replacement of cement and to evaluate bone healing. Follow-up ranged from 52 to 966 days (median, 628 days).
Persistent calcium phosphate cement was identified in 15 of 18 patients on follow-up CT chest scans. The rate of cement absorption was not directly proportional to the postoperative follow-up time. Three patients had complete reabsorption of all calcium phosphate cement on follow-up CT scan. No patient demonstrated radiographic evidence of osteomyelitis or sternal infection. One person operated on emergently, who was on Plavix (Bristol-Myers Squibb, New York, NY), had to be explored for bleeding due to a coagulopathy unrelated to his sternal bleeding. At the time of exploration for bleeding, the calcium phosphate cement was easily removed from the sternum and appeared to have no adhesive properties. All 12 patients who had two CT chest scans far enough apart to determine bony replacement of the calcium phosphate cement revealed robust replacement of the cement with new bone formation. Their sternal bone densities consistently increased up to their last CT chest scan.
Comparing CT scans from the same patient revealed calcium phosphate cement was maximally absorbed by 1 month after surgery. After the first month after surgery, the rate of cement absorption appeared to be slow. Most patients were left with a thin discontinuous strip of cement visible in the midline that persisted despite the majority of cement having been reabsorbed from the lateral sternal marrow and the cortex of the sternum having healed. There was no tendency for sternums that required greater amounts of cements to have delayed replacement by bone. Bone replacement after the first month was patient specific. However, sternal healing persisted through the follow-up period on serial CT chest scans. Sternal step-offs and gaps were not uncommon. Sternal gaps did not appear to be related to the presence or absence of Callos.
Five patients had preoperative CT chest scans for evaluation. Postoperative bone densities were improved in each patient compared with their preoperative bone density. The average preoperative bone density (using bone density images) was –33.1 Hounsfield units (standard deviation 36.09). Postoperative bone densities averaged 248.56 Hounsfield units (standard deviation 149.8) (Figs 3A–3C). Using a two-tailed Student's t test for two samples of equal variances, the likelihood of these sternal bone densities being of similar groups was p = 0.0063.
View larger version (72K):
[in this window]
[in a new window]
|
Fig 3. (A) Preoperative computed tomographic chest scan using bone windows. The elliptical area measures 26.7 Hounsfield Units. (B) Computed tomographic chest scan of the same patient on postoperative day 31 reveals a small amount of retained cement and improved Hounsfield Units of 275.1. (C) Computed tomographic chest scan of same patient on postoperative day 508 reveals complete absorption of Callos and increased sternal Hounsfield Units of 418.4.
|
|
|
Comment
|
|---|
The most important finding in our study was the greater bone density seen at follow-up in every patient who had a preoperative CT chest scan for comparison (p = 0.006). In these patients, we were able to demonstrate denser new bone formation compared with what was present before surgery. Also in patients who had at least two postoperative CT chest scans, bone density also improved on follow-up scans. Presumably denser bone implies more bone present after Callos use. Whether this means improved blood supply, improved sternal strength, and improved resistance to infection is not known. Whether this is a long-lasting effect is also unknown, but it appears to be at intermediate follow-up. Whether bone marrow production occurs is also unclear. Clearly, bone healing is not impeded by the cement and appears to be encouraged.
Callos is a calcium phosphate cement that is Food and Drug Administration approved for use as a bone filler in orthopedic surgery to fill bony voids of the skeletal system [3, 4]. A literature review showed that this bone void filler has been used in fractures that typically have not permitted weight bearing for a long time (tibial pateau and calcaneal fractures) [3, 4]. As a result of its superior compressive strength to normal bone, patients can bear weight earlier, promoting quicker recovery. Callos cures rapidly without exothermic reaction to form carbonated apatite that corresponds to the mineral phase of bone. When implanted, Callos bone cement is known to be osteoconductive with no adverse tissue reactions. The implanted area remodels through normal remodeling by osteoclastic cell-mediated absorption and osteoblastic-mediated new bone formation [5]. Frankenburg and colleagues [6] demonstrated in dogs both osteoconductive and biocompatible properties. There was no evidence of fibrosis or inflammation at any interval of time. Vascular penetration in the cement was evident, and many vessels were found to have circumferential lamellae of bone that resembled developing haversian systems in histiologic sections. The haversian bone was similar to normal bone remodeling. This study clearly demonstrated that calcium phosphate cement is both osteoconductive and remodeled, with simultaneous replacement by bone through the normal osteoclastic-osteoblastic coupling.
Several other agents are currently used clinically to tamponade sternal bleeding [7–10]. They are all foreign bodies, except Viostat (Vivolution, Birkeroed, Denmark) [9]. None are promoted to be used in large volume. Those that do not biodegrade can initiate infection at a later date. Moreover, none become incorporated by the body into bone as Callos does after its use. Bone wax is still a better first line product to control bleeding during most open heart surgeries, but its use would be ill advised in our patient study group. In patients such as ours, with large defects in their sternum, huge amounts of bone wax would have been required to control bleeding. Bone wax use is associated with foreign body granulomas [8], and a higher incidence of sternal dehiscence, as well as deep wound infections [2]. Its primary function in orthopedic surgery is to inhibit bone growth. Callos appears to have the opposite effect on the bone.
We found that new bone consistently replaced the calcium phosphate cement. There was unambiguous evidence of bone replacement of Callos in all patients with at least two CT chest scans available for review. This absorption replacement with bone continues through at least the intermediate follow-up period. The majority of Callos cement was reabsorbed within the first 30 days after open heart surgery. Indeed, one patient demonstrated almost complete absorption within 9 days of surgery. When Callos remodels, first collagenous "osteoid" formation occurs (nonmineralized colloid scaffold), then later mineralization occurs. This phenomenon is typically seen in almost all orthopedic fracture healing. Typically one sees a zone of vacant bone look around a fracture. Later, mineralization occurs and radiographic healing is evident. Similarly, when Callos is used, a zone of bone void occurs around the cement. Histologic analysis of this colloid material has confirmed osteoid formation [5]. The osteoid formation is not recognized when using CT scans, because it is not mineralized bone at this point. This is likely the reason why patients in our study had solid sternums on clinical examination while their CT chest scans demonstrated absorbed Callos, but not bony sternal union.
The limitations of our study are that preoperative CT chest scans were not obtained in all patients and we do not have a control group. This would allow us to confirm the finding of denser new bone formation in a larger patient population. Another limitation of our study is that we did not perform CT chest scans at uniform time intervals. This would expose patients to a greater radiation exposure and cancer risk. However, such scans would allow us to determine if all adults absorb Callos at similar rates and deposit bone at like times. Our results suggest that Callos is absorbed quickly but not completely, and bone formation takes longer to start, but is long lasting. After calcium phosphate cement use, new bone populates the sternum and appears to have greater bone density.
|
Disclosures and Freedom of Investigation
|
|---|
Dr Muehrcke is a clinical advisor to Skeletal Kinetics. No funds were received to perform this study. Skeletal Kinetics, LLC (Cupertino, CA) provided financial support to compensate the costs of the CT scans directly to Flagler Hospital and to reimburse patients directly for gas money. All products were purchased by the hospital, and the authors of this study had full control of the design of the study, methods used, outcome measurements, analysis of data, and production of the written report.
|
Footnotes
|
|---|
Disclaimer The Society of Thoracic Surgeons, the Southern Thoracic Surgical Association, and The Annals of Thoracic Surgery neither endorse nor discourage use of the new technology described in this article.
|
References
|
|---|
- Muehrcke DD, Barberi P, Shimp WM. Calcium phosphate cements to control bleeding in osteoporotic sternums Ann Thoracic Surg 2007;84:259-262.[Abstract/Free Full Text]
- Harjula A, Jarvinen A. Postoperative median sternotomy dehiscence Scand J Thorac Cardiovasc Surg 1983;19:277-281.
- Schildhauer TA, Bauer TW, Josten C, Muhr J. Open reduction and augmentation of internal fixation with an injectable skeletal cement for the treatment of complex calcaneal fractures J Orthop Trauma 2000;14:309-317.[Medline]
- Lobenhoffer P, Gerich T, Witte F, Tscherne H. Use of injectable calcium phosphate bone cement in the treatment of tibial pateau fractures: a prospective study of twenty-six cases with twenty-month mean follow-up J Orthop Trauma 2002;16:143-149.[Medline]
- Yetkiner DN, Delaney D, Constantz BR, et al. In vitro and in vivo evaluation of two calcium phosphate cementsProceedings of the 50th Annual Meeting of the Orthopedic Research Society, San Francisco, CA, March 7–10, Poster 1520. 2004.
- Frankenburg EP, Goldstein SA, Bauer TW, Harris SA, Poser RD. Biomechanical and histological evaluation of a calcium phosphate cement J Bone Joint Surg Am 1998;80:1112-1124.[Medline]
- Blanche C, Shaux A. The use of absorbable microfibrillation collagen to control sternal bone marrow bleeding Int Surg 1988;73:42-43.[Medline]
- Anfinsen OG, Sudmann B, Rait M, Bang G, Sudmann E. Complications secondary to the use of standard bone wax in seven patients J Foot Ankle Surg 1992;32:505-508.
- Kjaergard HK, Trumbull HR. Bleeding from the sternal marrow can be stopped using Vivostat patient-derived fibrin sealant Ann Thorac Surg 2000;69:1173-1175.[Abstract/Free Full Text]
- Wellisz T, Amstrong JK, Cambridege J, Fisher TC. Ostene, a new water-soluble bone hemostasis agent J Craniofac Surg 2006;17:420-425.[Medline]
This article has been cited by other articles:
|
|
|
|
 
I. Gallo, A. Saenz, E. Artinano, and J. Esquide
Autologous platelet-rich plasma: effect on sternal healing in the sheep model
Interact CardioVasc Thorac Surg,
September 1, 2010;
11(3):
223 - 225.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
