Effect of Nandrolone, Calcium-D and Vitamin C on Fracture Union

AUTHORS

Ali Yeganeh 1 , Bahram Boddouhi 1 , Roozbeh Taghavi 2 , Mahzad Saidifard 3 , Abolfazl Bagheri Fard 4 , Mehdi Moghtadaei 1 , *

1 Department of Orthopedics, Rasool-e-Akram Hospital, Iran University of Medical Science, Tehran, IR Iran

2 Department of Orthopedic Surgery, Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, IR Iran

3 Department of Anesthesiology, Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

4 Department of Orthopedics, Shafa Yahyaeian Hospital, Iran University of Medical Science, Tehran, IR Iran

How to Cite: Yeganeh A, Boddouhi B, Taghavi R, Saidifard M, Bagheri Fard A, et al. Effect of Nandrolone, Calcium-D and Vitamin C on Fracture Union, Iran Red Crescent Med J. 2015 ; 17(9):e13942. doi: 10.5812/ircmj.13942.

ARTICLE INFORMATION

Iranian Red Crescent Medical Journal: 17 (9); e13942
Published Online: September 1, 2015
Article Type: Research Article
Received: July 31, 2013
Revised: November 11, 2013
Accepted: June 24, 2015
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Abstract

Background: Delay union and nonunion is one of the most common fractures complications of extremities in humans. There are several factors influencing normal process of bone union. Nutrition is an important factor in this process.

Objectives: In this study we aimed to observe the effect of nandrolone, calcium-D and vitamin C on the process of healing of fractures.

Patients and Methods: This study included 139 male patients, aged 18 to 50 years, with fracture of the shaft of tibia and fibula that were treated surgically with intramedullary nailing. These patients were randomly divided to four groups; group 1 received 25 mg of nandrolone decanoate via intramuscular injection every three weeks. Patients of group 2 received 1000 mg of calcium carbonate plus 400 international units of vitamin D3 per day. Patients of group 3 received 1000 mg of vitamin C per day, and group 4 served as the control group and didn’t receive any drug. These groups were compared according to radiographic and clinical criteria for fracture union.

Results: Patients in the nandrolone group showed better union in the first three months after surgery than the control group, with the difference being significant. There was no significant difference in calcium-D and vitamin C groups with respect to the control group.

Conclusions: Nandrolone in the first three months after surgery can accelerate fracture union yet calcium plus vitamin D or vitamin C has no effect on fracture union.

Keywords

Nandrolone Calcium Vitamin C Fracture Union

Copyright © 2015, Iranian Red Crescent Medical Journal. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

1. Background

Delay union and nonunion are challenging complications in orthopedic surgeries, which affect both quality of life of the patients and cost of treatments. Many factors can influence the normal process of bone healing. Hormones, nutrition and supplements are the most important factors amongst these factors (1, 2). Calcium and vitamin C are the most important supplements for the normal process of bone healing. Calcium makes up the primary structure of bones and vitamin C is a cofactor for hydroxylation of proline and lysine amino acids that are vital for collagen synthesis, the scaffold for calcium deposit in callus formation, and bone structure (3, 4). In one experimental study on rats, it was shown that union of fractured bone in the presence of low vitamin C diet resulted in callus formation with lower mechanical resistance and histological grade of bone healing than in rich vitamin C diets (4). Among hormones, androgenic hormones are the most important factors for union of fractured bones, and nandrolone is an injection form of anabolic steroids.

2. Objectives

There are many studies on the anti-osteoporotic effect of nandrolone (5-7) thus we decided to perform this study to observe the effect of nandrolone on healing of fractured bones.

3. Patients and Methods

All male patients aged 18 to 50 years with fracture of the shaft of tibia and fibula, referred to the Rasool hospital, from June 2008 to June 2011 were included in our research. All patients were treated surgically with closed reamed static lock intramedullary nailing without fixation of fibula. Our exclusion criteria were; having open fractures, pathological fractures, previous fracture of the bones, multiple fractures in the same or other extremities, multiple traumas with head or abdomen or other organ injuries, diabetes mellitus or other chronic disorders such as rheumatoid arthritis, metaphyseal or intra-articular fractures or any fracture patterns that could not be fixed with the closed intramedullary nailing method, any indication for fixation of fibula in addition to tibia, addiction to any drugs or narcotics, any contraindication for use of nandrolone, calcium and vitamin C.

Thus after exclusion of the patients who met the above-mentioned exclusion criteria, 160 male patients with fracture of the shaft of tibia and fibula remained in the study and were divided to four groups:

1- Patients in the nandrolone group received 25 mg of nandrolone decanoate via intramuscular injection every three weeks;

2- Patients in the calcium group received 1000 mg of calcium carbonate plus 400 IU of vitamin D3, orally, per day;

3- Patients in the vitamin C group received 1000 mg of vitamin C, orally, per day;

4- Patients in the control group received no drugs.

These mentioned drugs were started 48 hours after surgery and were continued for three months. We used an anatomic classification for fracture location as proximal, middle or distal fracture of the shaft of tibia and also used the Winquist and Hansen classification (8) for severity of comminution of the fractures, and based on this we divided our patients to two subcategories: those with less than 50% comminution, which means cortical contact between the proximal and distal segments was at least 50% and those with greater than 50% commination, which means cortical contact between proximal and distal segments was less than 50%. All patients were treated surgically with closed reamed static lock intramedullary nailing of the tibia without fixation of fibula. For obtaining more homologue groups, if one patient had an indication for fixation of fibula, he or she was excluded from the study. After surgery all patients received 1 g of cefazolin every eight hours intravenously for 24 hours and acetaminophen tablet or ampule as an analgesic if required. Forty-eight hours after surgery, the purpose of the study was explained to the patients and if they agreed to participate, they were randomly allocated to one of the four groups and received their first dose of supplement followed by their discharge from the hospital. The first visit of patients was two weeks after surgery for observation of the wound and removal suture and then at six and 12 weeks after surgery for radiographic assessment of union and after that radiography was performed monthly until complete union was achieved. Our criteria for union were bridging callus in at least three of the four cortices in the anteroposterior and lateral radiographs (9) and no tenderness in the fracture site and painless weight bearing on the fractured leg (10). If these criteria were not achieved until the fifth month after surgery yet radiographs showed progression of union we used the term ‘delayed union’ and if radiographs showed no progression of union we used the term ‘nonunion’.

Results were analyzed with the SPSS 22 software. We used one-way Analysis of Variance (ANOVA) test for comparison of patient’s age between groups and chi-square and binary logistic for comparison of union in different groups and subgroups.

4. Results

Twenty-one of 160 patients were excluded from the study because of different reasons: five patients because of using herbal material to accelerate the union, four patients because of infection that required several surgical operations, one patient because of discontinuing calcium due to renal colic, one patient because of discontinuing Nandrolone due to severe increase in sexual habits, one patient because of another trauma leading to bending of the intramedullary nail that required revision surgery, five patients because of lack of timely referral for radiographies and four patients because of dissatisfaction with the use of supplements. The other 139 patients remained in the study and their specifications are listed in Table 1.

Table 1. Demographic Information of Patients a
VariablesNandrolone GroupCalcium GroupVitamin C GroupControl GroupP Value
Job
Employee13 (4.6)7 (20.6)0 (0)6 (16.7)0.02
Self-employed14 (43.8)23 (67.6)31 (91.2)26 (72.2)
Other5 (15.6)24 (11.8)3 (8.8)4 (11.1)
Mechanism of injury
Crash25 (78.1)30 (88.2)33 (97.1)30 (83.3)0.169
Sports and strife4 (12.5)2 (5.9)1 (2.9)1 (2.8)
Other3 (9.4)2 (5.9)0 (0)5 (13.9)
Status of Fibula0.328
Broken32 (100)33 (97.1)34 (100)34 (94.4)
Intact0 (0)1 (2.9)0 (0)2 (5.6)
Treatment of Fibula0.873
Not treated 31 (96.9)32 (94.1)32 (94.1)35 (97.2)
Plate 1 (3.1)2 (5.9)2 (5.9)1 (2.8)
Status of peroneal nerve0.424
Intact32 (100)34 (100)34 (100)35 (97.2)
Damaged0 (0)0 (0)0 (0)1 (2.8)

a Values are presented as No. (%).

The 6th week radiographs of the groups showed better union in the nandrolone group than the control group. In this group 20 patients (62.5%) achieved radiographic and clinical criteria of union (P = 0.023, OR = 3.136) while patients in the calcium and vitamin C groups were not significantly different from those in the control group regarding union formation (P = 0.77 and P = 0.56, respectively). Twenty-six patients (81.3%) in the nandrolone group had achieved union by the 12th week, which was significantly better than the control group (P = 0.033, OR = 3.302) yet again patients in the calcium and vitamin C groups were not significantly different from the controls (P = 0.34 and P = 0.38, respectively). Four months after surgery, the difference of union in the nandrolone group and the control group was marginal (P = 0.073) yet the patients in the calcium and vitamin C groups were not significantly different when compared to the controls (P = 0.52 and P = 0.63, respectively). Five months after surgery, the difference in union between the three supplement groups and the control group was not significant (P > 0.05 for all groups). Five months after surgery, two patients in the nandrolone group (6.3%), five patients in the calcium group (14.7%), six patients in the vitamin C group (16.7%) and seven patients in the control group (18.9%) developed delayed union. Furthermore, one patient in the nandrolone group (3.1%), two patients in the calcium group (5.9%), three patients in the vitamin C group (8.3%) and two patients in the control group (5.4%) required surgery due to nonunion. These differences between groups were not significant. We analyzed the rate of union in each group based on the anatomic location of the fracture and degree of comminution of the bone and could not find a significant difference in these subgroups.

5. Discussion

To the best of our knowledge, there is no study on the effect of nandrolone in fracture healing in humans. Ahmad (11) in a radiographic and histologic study on rabbits showed that nandrolone decanoate can lead to better union of fracture when compared to the control group. There are many researches about the effect of nandrolone in humans yet the majority of them are about the effect of nandrolone on bone mineral density and osteoporosis (5-7, 12). In this study we showed that nandrolone in the first three months after fracture can accelerate union of the bone. The rate of delay union and nonunion in the nandrolone group was less than the other groups yet this difference was not statistically significant. This may be due to the sample size so repeating this study with larger sample sizes may result in significant differences.

The effect of calcium on fractures is controversial. Bischoff-Ferrari (13) in a meta-analysis claimed that calcium has no effect on prevention of hip fractures. On the other hand, Avenell (14) and Boonen (15) in another meta-analysis suggested that calcium and vitamin D have preventive effects on hip fractures. Dawson-Hughes (16) in a three-year-prospective study on males and females 65 years of age or older showed that dietary supplementation with calcium and vitamin D could reduce bone loss and the incidence of non-vertebral fractures. On the other hand, Orwoll (17) in a Double-blinded, placebo-controlled study on 30 to 87-year-old males concluded that bone loss at both axial and appendicular skeleton could not be prevented by calcium and vitamin D supplementation in a well-nourished population. There are many studies on the effect of calcium on the prevalence or prevention of fractures yet we could not find any comprehensive study about the effect of calcium on fracture union. Kolb (18) in a study on 94 postmenopausal females with distal radius fractures concluded that calcium and parathyroid hormone serum levels within physiological ranges are required for appropriate callus formation. In our study, calcium plus vitamin D had no effect on fracture union. It is important to mention that we included 18 to 50 year-old males only to exclude confounders such as osteoporosis and obtained more homologue samples yet most of the previous studies were on osteoporotic populations 65 years age and older. Thus as Orwoll and Kolb concluded, it seems that in the normal range of calcium and parathyroid hormone, additional use of calcium and vitamin D has no more effect on fracture healing.

There are many animal studies about the effect of vitamin C on fracture healing. Yilmaz (19) in a study on 16 rats concluded that one dose injection of vitamin C can accelerate the healing process of bone and Sarisozen (20) in a study on 48 rats indicated that vitamin C can accelerate fracture healing. Although there are many human studies about the effect of vitamin C on tissue healing, pressure sores and common cold (21, 22), as well as its antioxidant (23) and anti-atherosclerosis effects (24, 25) (26), studies about the effect of vitamin C on fracture healing in humans are a few. In this study, we collected homologue samples and showed that vitamin C supplements have no effect on fracture union.

We could not find significant correlations between union rate and anatomic location of the fracture in this study and we could not find significant correlations between union rate and severity of comminution of the fracture although one can expect decreased rate of union with increased comminution resulting from more bone and soft tissue injury. Table 1 indicates small sample sizes in subgroups so we recommend repeating this study with two groups instead of four with more samples in subgroups for obtaining better results.

Intramuscular injection of nandrolone decanoate in the first three months of fracture treatment could result in acceleration of fracture union yet use of calcium plus vitamin D or use of vitamin C supplementations does not seem to have an effect on fracture healing.

Footnote

References

  • 1.

    Jensen JE, Jensen TG, Smith TK, Johnston DA, Dudrick SJ. Nutrition in orthopaedic surgery. J Bone Joint Surg Am. 1982; 64(9) : 1263 -72 [PubMed]

  • 2.

    Cederholm T, Hedstrom M. Nutritional treatment of bone fracture. Curr Opin Clin Nutr Metab Care. 2005; 8(4) : 377 -81 [PubMed]

  • 3.

    Naidu KA. Vitamin C in human health and disease is still a mystery? An overview. Nutr J. 2003; 2 : 7 [DOI][PubMed]

  • 4.

    Alcantara-Martos T, Delgado-Martinez AD, Vega MV, Carrascal MT, Munuera-Martinez L. Effect of vitamin C on fracture healing in elderly Osteogenic Disorder Shionogi rats. J Bone Joint Surg Br. 2007; 89(3) : 402 -7 [DOI][PubMed]

  • 5.

    Flicker L, Hopper JL, Larkins RG, Lichtenstein M, Buirski G, Wark JD. Nandrolone decanoate and intranasal calcitonin as therapy in established osteoporosis. Osteoporos Int. 1997; 7(1) : 29 -35 [PubMed]

  • 6.

    Hedstrom M, Sjoberg K, Brosjo E, Astrom K, Sjoberg H, Dalen N. Positive effects of anabolic steroids, vitamin D and calcium on muscle mass, bone mineral density and clinical function after a hip fracture. A randomised study of 63 women. J Bone Joint Surg Br. 2002; 84(4) : 497 -503 [PubMed]

  • 7.

    Passeri M, Pedrazzoni M, Pioli G, Butturini L, Ruys AH, Cortenraad MG. Effects of nandrolone decanoate on bone mass in established osteoporosis. Maturitas. 1993; 17(3) : 211 -9 [PubMed]

  • 8.

    Winquist RA, Hansen SJ. Comminuted fractures of the femoral shaft treated by intramedullary nailing. Orthop Clin North Am. 1980; 11(3) : 633 -48 [PubMed]

  • 9.

    Rockwood & Green`s fractures in adults. 2010; : 641 -63

  • 10.

    Sarmiento A, Sharpe FE, Ebramzadeh E, Normand P, Shankwiler J. Factors influencing the outcome of closed tibial fractures treated with functional bracing. Clin Orthop Relat Res. 1995; (315) : 8 -24 [PubMed]

  • 11.

    Ahmad F, Yunus SM, Asghar A, Faruqi NA. Influence of anabolic steroid on tibial fracture healing in rabbits - a study on experimental model. J Clin Diagn Res. 2013; 7(1) : 93 -6 [DOI][PubMed]

  • 12.

    Tengstrand B, Cederholm T, Soderqvist A, Tidermark J. Effects of protein-rich supplementation and nandrolone on bone tissue after a hip fracture. Clin Nutr. 2007; 26(4) : 460 -5 [DOI][PubMed]

  • 13.

    Bischoff-Ferrari HA, Dawson-Hughes B, Baron JA, Burckhardt P, Li R, Spiegelman D, et al. Calcium intake and hip fracture risk in men and women: a meta-analysis of prospective cohort studies and randomized controlled trials. Am J Clin Nutr. 2007; 86(6) : 1780 -90 [PubMed]

  • 14.

    Avenell A, Gillespie WJ, Gillespie LD, O'Connell D, Avenell A. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. The Cochrane database of systematic rev. 2005; 3 : 227 -32 [DOI]

  • 15.

    Boonen S, Lips P, Bouillon R, Bischoff-Ferrari HA, Vanderschueren D, Haentjens P. Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab. 2007; 92(4) : 1415 -23 [DOI][PubMed]

  • 16.

    Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med. 1997; 337(10) : 670 -6 [DOI][PubMed]

  • 17.

    Orwoll ES, Oviatt SK, McClung MR, Deftos LJ, Sexton G. The rate of bone mineral loss in normal men and the effects of calcium and cholecalciferol supplementation. Ann Intern Med. 1990; 112(1) : 29 -34 [PubMed]

  • 18.

    Kolb JP, Schilling AF, Bischoff J, Novo de Oliveira A, Spiro A, Hoffmann M, et al. Calcium homeostasis influences radiological fracture healing in postmenopausal women. Arch Orthop Trauma Surg. 2013; 133(2) : 187 -92 [DOI][PubMed]

  • 19.

    Yilmaz C, Erdemli E, Selek H, Kinik H, Arikan M, Erdemli B. The contribution of vitamin C to healing of experimental fractures. Arch Orthop Trauma Surg. 2001; 121(7) : 426 -8 [PubMed]

  • 20.

    Sarisozen B, Durak K, Dincer G, Bilgen OF. The effects of vitamins E and C on fracture healing in rats. J Int Med Res. 2002; 30(3) : 309 -13 [PubMed]

  • 21.

    Goode HF, Burns E, Walker BE. Vitamin C depletion and pressure sores in elderly patients with femoral neck fracture. BMJ. 1992; 305(6859) : 925 -7 [PubMed]

  • 22.

    Hellman L, Burns JJ. Metabolism of L-ascorbic acid-1-C14 in man. J Biol Chem. 1958; 230(2) : 923 -30 [PubMed]

  • 23.

    Cameron E, Pauling L, Leibovitz B. Ascorbic acid and cancer: a review. Cancer Res. 1979; 39(3) : 663 -81 [PubMed]

  • 24.

    Knekt P, Reunanen A, Jarvinen R, Seppanen R, Heliovaara M, Aromaa A. Antioxidant vitamin intake and coronary mortality in a longitudinal population study. Am J Epidemiol. 1994; 139(12) : 1180 -9 [PubMed]

  • 25.

    Osganian SK, Stampfer MJ, Rimm E, Spiegelman D, Hu FB, Manson JE, et al. Vitamin C and risk of coronary heart disease in women. J Am Coll Cardiol. 2003; 42(2) : 246 -52 [PubMed]

  • 26.

    Hemilä H, Chalker E, Hemilä H. 2013; [DOI]

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