- Email: [email protected]
Use of teriparatide in osteoporotic fracture patients
Injury, Int. J. Care Injured 47 S1 (2016) S36–S38
Contents lists available at ScienceDirect
Injury j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i n j u r y
Use of teriparatide in osteoporotic fracture patients Cory Collingea,*, Juan Favelab a b
Department of Orthopedic Surgery, Vanderbilt University, Medical Center East, Nashville, TN, USA University of Texas, Southwestern Medical School, Dallas, TX, USA
KEYWORDS
ABSTRACT
teriparatite fragility anabolic effect osteoporosis
Teriparatide [PTH (1–34)] is a genetically engineered analog of human parathyroid hormone that acts as an anabolic drug by increasing activity in both osteoblasts and osteoclasts. Intermittent (once-daily) doses of teriparatide seem to stimulate osteoblast activity and therefore result in a net increase of bone formation. It is recommended for use in post-menopausal women (PMW), men with hypogonadal osteoporosis, as well as men and women with glucocorticoid-induced osteoporosis. In vivo studies have generated important findings regarding teriparatide’s role in the enhancement of fracture healing. The intention of this article is to review the clinical findings of teriparatide to stimulate fracture healing. The drug was shown in a prospective randomized, double blind study to achieve earlier radiographic cortical bridging of three of four cortices (7.4 weeks) compared to patients who were assigned to the placebo group (9.1 weeks). Another study compared mean time for healing and functional outcome in two groups of elderly women who had suffered osteoporotic pelvic fractures: one group received daily 100 g parathyroid hormone (1–84) injections, while the other group received no treatment. Patients who received the PTH (1–84) injections accelerated radiographic and clinical fracture healing (7.8 weeks) when compared to patients who received no treatment (12.6 weeks, p<0.001). Numerous case series state the safety and potential benefits of teriparatide use in patients recovering from fractures. In the following scenarios, teriparatide might be considered in patients with osteoporosis and a fracture: (1) patients with severe osteoporosis with use of bisphosphonates for a number of years with a fracture not expected to predictably unite, e.g. atypical femur fracture or open tibia fracture, (2) in cases where an osteoporotic patient has failed fracture healing and is considering surgical treatment e.g. non-union surgery. It seems prudent to reevaluate these patients frequently and reconsider which drug class of osteoporotic drug is best for the patient. Finally, it must be stressed that we do not recommend teriparatide in osteoporotic patients that may be well treated with bisphosphonates and a fracture is expected to heal uneventfully, nor when patients with metabolically normal bone have a fracture. © 2016 Elsevier Ltd. All rights reserved.
Introduction Teriparatide [PTH (1–34)] is a genetically engineered analog of human parathyroid hormone that is used to treat osteoporosis in patients who are at a high risk for fracture. This drug is recommended for use in post-menopausal women (PMW), men with hypogonadal osteoporosis, as well as men and women with glucocorticoid-induced osteoporosis [1–3]. Administration of teriparatide stimulates new bone formation resulting in increased bone strength and density. Teriparatide’s mechanism of action is similar to that of endogenous human parathyroid hormone (PTH); both hormones bind to the same cell-surface receptors on osteoblasts and thus have the same physiological effects on bone and kidney. As opposed to anti-resorptive drugs (e.g. bisphosphonates), which increase bone density and
* Corresponding author at: Department of Orthopedic Surgery, Vanderbilt University, Medical Center East, South Tower, Suite 4200, Nashville, TN 37235, USA. E-mail address: [email protected] (C. Collinge). 0020-1383/© 2016 Elsevier Ltd. All rights reserved.
strength by inhibiting osteoclast activity, anabolic drugs like teriparatide work by increasing activity in both osteoblasts and osteoclasts. Intermittent (once-daily) doses of teriparatide seem to preferentially stimulate osteoblast activity and therefore result in a net increase of bone formation [4]. While teriparatide injections have proved to be an effective way of increasing bone mass and reducing fracture risk in patients with osteoporosis, recent findings suggest that teriparatide injections may also be used to enhance fracture healing [4–14]. Teriparatide and bone healing: basic science Animal studies have generated important findings regarding teriparatide’s role in the enhancement of fracture healing. One such study demonstrated that systemic administration of PTH (1–34) in rats that had undergone diaphyseal femur fractures led to an overall increase in bone mineral content and density, as well as an increase in bone strength when compared to rats that did not receive PTH (1–34) injections [5]. Recombinant human parathyroid hormone [hPTH (1-34)] similarly accelerated the
C. Collinge and J. Favela / Injury, Int. J. Care Injured 47 S1 (2016) S36–S38
S37
Fig. 1. Clinical case of an 81 year old woman with osteoporosis on a Bisphosphonate who tripped on a curb and fell experiencing an open Gustilo and Anderson type IIIB tibia fracture with bone loss (a,b). She was felt to be at high risk for failure and need for amputation. The patient was treated with a medial locking plate, BMP-2 (Infuse®, Medtronic, Fridley, MN), and local rotation flap (b). Bisphosphonate medicine was discontinued and the patient was started on daily Teriparatide (Forteo®, Eli Lilly, Indianapolis, IN). Final radiographs of healed tibia (c). Patient was ambulatory with occasional use of an assistive cane.
fracture healing process in monkeys with surgically-induced femur fractures by decreasing the size and increasing degree of mineralization of the fracture callus; thus indicating that PTH (1–34) might also accelerate the healing process in human fractures [4]. In a similar study, researchers examined the effects of intermittent administration of parathyroid hormone on fracture healing in ovariectomized rats [12]. After inducing bilateral tibial shaft fractures in the rat models and then stabilizing them via intramedullary nailing with Kirschner wires, the animals were given daily doses of either saline, 17-estradiol, or recombinant PTH (1–84) for 30 consecutive days. Morphometric and mechanical analyses of fracture callus were used to assess fracture healing. The results of the study showed that intermittent administration of PTH increased the morphometric and mechanical parameters of fracture callus (callus length, callus diameter, ultimate load, ultimate stiffness, ultimate stress, etc.) [12]. Intermittent administration of PTH (1–34) also seems to have a positive influence on callus formation and mechanical strength of tibial fractures in rats [6]. After daily administration of 60 g PTH (1–34), 200 g PTH (1–34), and saline solution, rats that were given daily doses of 200 g experienced increases in both external callus volume as well as ultimate axial load. Finally, a group of researchers investigated the efficacy of a parathyroid hormone related protein (PTHrP) analog as systemic therapy for impaired bone healing in corticosteroid-treated rabbits [9]. A 1mm defect was created bilaterally in the ulnae of 30 rabbits and delayed healing was induced by administering daily prednisone injections beginning 2 months prior to killing the rabbits and continuing all the way up to the time of killing. At 6 weeks postinjury, 9 out of 10 rabbits in the experimental group had achieved radiographic union and only 2 out of 10 in the control (saline) group had achieved similar results in that same time period. PTHrP was shown to be an effective therapy for preventing impaired bone healing as it caused higher radiographic intensity, larger callus area, increased stiffness, and increased torque.
patients with osteoporosis (Fig. 1). In a prospective randomized, double blind study, Aspenberg et al. compared the effects of 20 and 40 g/day teriparatide injections versus placebo on the time to radiographic healing of distal radial fractures in postmenopausal women [7]. Radiographic evidence of complete cortical bridging in three of four cortices happened earlier for patients assigned to the teriparatide 20 g/day group (7.4 weeks) when compared to patients who were assigned to the placebo group (9.1 weeks). Another study compared mean time for healing and functional outcome in two groups of elderly women who had suffered osteoporotic pelvic fractures: one group received daily 100 g parathyroid hormone (1–84) injections, while the other group received no treatment [13]. Patients who received the PTH (1–84) injections accelerated radiographic and clinical fracture healing (7.8 weeks) when compared to patients who received no treatment (12.6 weeks, p<0.001). Numerous case series state the safety and potential benefits of teriparatide use in patients recovering from fractures. One such study describes the effects of daily 20 g teriparatide injections on a cohort of 145 patients who had failed previous fracture healing, i.e. presented some form of nonunion or delayed union, or were high-risk candidates for healing acute fractures [10]. Ninety-three percent of patients demonstrated radiographic and clinical union of their fractures, and only 3% of patients failed to see early progression to clinical and radiographic union. Additional case studies have shown that delayed healing in acute and stress fractures were well treated with daily teriparatide injections along with a Vitamin/ calcium citrate supplement. Raghavan et al. showed that two women with slow healing metatarsal stress fracture healed within four weeks of starting PTH therapy [14]. Likewise, Borges et al. presents the case of an 84-year-old woman with a transtrochanteric femur fracture that showed slow progression of fracture healing one month postsurgery and healed very quickly after initiating daily 20 g doses of teriparatide [8].
Teriparatide and bone healing: clinical research
Recommendations for teriparatide usage in fracture patients
The clinical benefits of teriparatide are likely to extend beyond its approved use as a fracture prevention drug in
The decision to use teriparatide in patients with moderate or severe osteoporosis and a fracture must be considered
S38
C. Collinge and J. Favela / Injury, Int. J. Care Injured 47 S1 (2016) S36–S38
thoughtfully, as there is no cookbook answer for its use in this setting. Despite some promising results in animal studies and positive clinical support, regulatory bodies such as the U.S. Food and Drug Administration do not currently approve teriparatide for the enhancement of fracture healing. There are a few scenarios where teriparatide might be considered in patients with osteoporosis and a fracture. First, it might be considered when a patient with severe osteoporosis has been taking bisphosphonates for a number of years and has a fracture not expected to predictably unite, e.g. atypical femur fracture or open tibia fracture. Teriparatide could be used to treat the osteoporosis, while providing a vacation from bisphosphonates, and potentially providing a trophic effect on fracture healing. The drug also might be considered in cases where an osteoporotic patient has failed fracture healing and is considering surgical treatment e.g. non-union surgery. It seems prudent to reevaluate these patients frequently and reconsider which drug class of osteoporotic drug is best for the patient. Finally, it must be stressed that we do not recommend teriparatide in osteoporotic patients that may be well treated with bisphosphonates and a fracture is expected to heal uneventfully, nor when patients with metabolically normal bone have a fracture. Research shows that dosing may influence teriparatide’s anabolic effect on bone healing [5,7,10,11]; 20 g per day given subcutaneously appears beneficial for stimulating union, while a 40 g daily injection has little to no effect on the time to fracture healing. There is some controversy as to how long patients should continue to use teriparatide after their fracture has been treated. While the recommended use is for a maximum period of 2 years, it remains unclear as to whether the patient should take teriparatide only until the fracture has healed or whether he/ she should take the drug for the entire two year period. Several factors must be taken into consideration before being able to make this decision. Contraindications to teriparatide treatment include hypersensitivity to PTH, PTH (1–34), or any of the drug’s excipients. There is also a potential risk of osteosarcoma associated with the use of teriparatide; therefore patients at an increased baseline risk of osteosarcoma (Paget’s disease of bone, pediatric patients with open epiphyses, and prior external beam or implant radiation therapy involving the skeleton) should avoid this form of treatment. Teriparatide injections also pose a significant financial burden, thus the patient’s ability to manage the cost of this therapy is likely to determine how long he/she will receive this treatment. Additionally, one must carry out a thorough assessment of the patient’s response to the drug, making sure that there are no serious side effects threatening the patient’s well-being, both now and in the future. Ultimately, the decision to continue teriparatide treatment up to the recommended last page reference
2-year period is a complex one and it involves careful analysis of the patient’s entire medical history. There are currently no known alternatives to teriparatide; however, there are many ongoing studies and clinical trials testing the efficacy of new drugs that may become available in a short period of time. Conflict of interest The authors have no conflicts of interest relating to the subject matter discussed in this manuscript. They have received no support of any kind in its creation. References [1] Deal C, Gideon J. Recombinant human PTH 1-34 (Forteo): an anabolic drug for osteoporosis. Cleve Clin J Med 2003;70:585–6, 589–90, 592–4 passim. [2] http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=aae667c5-381f4f92-93df-2ed6158d07b0. Accessed Dec 20, 2014. [3] http://www.uptodate.com/contents/parathyroid-hormone-therapy-for-osteoporosis. Accessed Dec 20, 2014. [4] Manabe T, Mori S, Mashiba T, Kaji Y, Iwata K, Komatsubara S, et al. Human parathyroid hormone (1-34) accelerates natural fracture healing process in the femoral osteotomy model of cynomolgus monkeys. Bone 2007;40:1475–82. [5] Alkhiary YM, Gerstenfeld LC, Krall E, Westmore M, Sato M, Mitlak BH, Einhorn TA. Enhancement of experimental fracture-healing by systemic administration of recombinant human parathyroid hormone (PTH 1-34). J Bone Joint Surg 2005;87:731–41. [6] Andreassen TT, Ejersted C, Oxlund H. Intermittent parathyroid hormone (1-34) treatment increases callus formation and mechanical strength of healing rat fractures. J Bone Miner Res 1999;14:960–8. [7] Aspenberg P, Genant HK, Johansson T, Nino AJ, See K, Krohn K, et al. Teriparatide for acceleration of fracture repair in humans: a prospective, randomized, double-blind study of 102 postmenopausal women with distal radial fractures. J Bone Miner Res 2010;25:404–14. [8] Borges JL, Freitas A, Bilezikian JP. Accelerated fracture healing with teriparatide. Arg Bras Endocrin Metabol 2013;57:153–6. [9] Bostrom MP, Gamradt SC, Asnis P, Vickery BH, Hill E, Avnur Z, Waters RV. Parathyroid hormone-related protein analog RS-66271 is an effective therapy for impaired bone healing in rabbits on corticosteroid therapy. Bone 2000;26:437–42. [10] Bukata SV, Kaback LA, Reynolds DG, O’Keefe RJ, Rosier RN. 1-34 PTH at physiologic doses in humans shows promise as a helpful adjuvant in difficult to heal fractures: An observational cohort of 145 patients. Presented at: 55th Annual Meeting of the Orthopaedic Research Society: February 25-28 2009. Las Vegas, NV. [11] Cipriano, CA, Issack PS, Shindle L, Werner CM, Helfet DL, Lane JM, et al. Recent advances toward the clinical application of PTH (1-34) in fracture healing. HSS J 2009;5:149–53. [12] Kim HW, Jahng JS. Effect of intermittent administration of parathyroid hormone on fracture healing in ovariectomized rats. Iowa Orthop J 1999;19:71–7. [13] Peichl P, Holzer LA, Maier R, Holzer G. Parathyroid hormone 1-84 accelerates fracture-healing in pubic bones of elderly osteoporotic women. J Bone Joint Surg 2011;93:1583–7. [14] Raghavan P, Chrisofides E. Role of teriparatide in accelerating metatarsal stress fractures healing: A case series and review of literature. Clinical Med Insights Endocrinol Diabetes 2012;5:39–45.
Contents lists available at ScienceDirect
Injury j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i n j u r y
Use of teriparatide in osteoporotic fracture patients Cory Collingea,*, Juan Favelab a b
Department of Orthopedic Surgery, Vanderbilt University, Medical Center East, Nashville, TN, USA University of Texas, Southwestern Medical School, Dallas, TX, USA
KEYWORDS
ABSTRACT
teriparatite fragility anabolic effect osteoporosis
Teriparatide [PTH (1–34)] is a genetically engineered analog of human parathyroid hormone that acts as an anabolic drug by increasing activity in both osteoblasts and osteoclasts. Intermittent (once-daily) doses of teriparatide seem to stimulate osteoblast activity and therefore result in a net increase of bone formation. It is recommended for use in post-menopausal women (PMW), men with hypogonadal osteoporosis, as well as men and women with glucocorticoid-induced osteoporosis. In vivo studies have generated important findings regarding teriparatide’s role in the enhancement of fracture healing. The intention of this article is to review the clinical findings of teriparatide to stimulate fracture healing. The drug was shown in a prospective randomized, double blind study to achieve earlier radiographic cortical bridging of three of four cortices (7.4 weeks) compared to patients who were assigned to the placebo group (9.1 weeks). Another study compared mean time for healing and functional outcome in two groups of elderly women who had suffered osteoporotic pelvic fractures: one group received daily 100 g parathyroid hormone (1–84) injections, while the other group received no treatment. Patients who received the PTH (1–84) injections accelerated radiographic and clinical fracture healing (7.8 weeks) when compared to patients who received no treatment (12.6 weeks, p<0.001). Numerous case series state the safety and potential benefits of teriparatide use in patients recovering from fractures. In the following scenarios, teriparatide might be considered in patients with osteoporosis and a fracture: (1) patients with severe osteoporosis with use of bisphosphonates for a number of years with a fracture not expected to predictably unite, e.g. atypical femur fracture or open tibia fracture, (2) in cases where an osteoporotic patient has failed fracture healing and is considering surgical treatment e.g. non-union surgery. It seems prudent to reevaluate these patients frequently and reconsider which drug class of osteoporotic drug is best for the patient. Finally, it must be stressed that we do not recommend teriparatide in osteoporotic patients that may be well treated with bisphosphonates and a fracture is expected to heal uneventfully, nor when patients with metabolically normal bone have a fracture. © 2016 Elsevier Ltd. All rights reserved.
Introduction Teriparatide [PTH (1–34)] is a genetically engineered analog of human parathyroid hormone that is used to treat osteoporosis in patients who are at a high risk for fracture. This drug is recommended for use in post-menopausal women (PMW), men with hypogonadal osteoporosis, as well as men and women with glucocorticoid-induced osteoporosis [1–3]. Administration of teriparatide stimulates new bone formation resulting in increased bone strength and density. Teriparatide’s mechanism of action is similar to that of endogenous human parathyroid hormone (PTH); both hormones bind to the same cell-surface receptors on osteoblasts and thus have the same physiological effects on bone and kidney. As opposed to anti-resorptive drugs (e.g. bisphosphonates), which increase bone density and
* Corresponding author at: Department of Orthopedic Surgery, Vanderbilt University, Medical Center East, South Tower, Suite 4200, Nashville, TN 37235, USA. E-mail address: [email protected] (C. Collinge). 0020-1383/© 2016 Elsevier Ltd. All rights reserved.
strength by inhibiting osteoclast activity, anabolic drugs like teriparatide work by increasing activity in both osteoblasts and osteoclasts. Intermittent (once-daily) doses of teriparatide seem to preferentially stimulate osteoblast activity and therefore result in a net increase of bone formation [4]. While teriparatide injections have proved to be an effective way of increasing bone mass and reducing fracture risk in patients with osteoporosis, recent findings suggest that teriparatide injections may also be used to enhance fracture healing [4–14]. Teriparatide and bone healing: basic science Animal studies have generated important findings regarding teriparatide’s role in the enhancement of fracture healing. One such study demonstrated that systemic administration of PTH (1–34) in rats that had undergone diaphyseal femur fractures led to an overall increase in bone mineral content and density, as well as an increase in bone strength when compared to rats that did not receive PTH (1–34) injections [5]. Recombinant human parathyroid hormone [hPTH (1-34)] similarly accelerated the
C. Collinge and J. Favela / Injury, Int. J. Care Injured 47 S1 (2016) S36–S38
S37
Fig. 1. Clinical case of an 81 year old woman with osteoporosis on a Bisphosphonate who tripped on a curb and fell experiencing an open Gustilo and Anderson type IIIB tibia fracture with bone loss (a,b). She was felt to be at high risk for failure and need for amputation. The patient was treated with a medial locking plate, BMP-2 (Infuse®, Medtronic, Fridley, MN), and local rotation flap (b). Bisphosphonate medicine was discontinued and the patient was started on daily Teriparatide (Forteo®, Eli Lilly, Indianapolis, IN). Final radiographs of healed tibia (c). Patient was ambulatory with occasional use of an assistive cane.
fracture healing process in monkeys with surgically-induced femur fractures by decreasing the size and increasing degree of mineralization of the fracture callus; thus indicating that PTH (1–34) might also accelerate the healing process in human fractures [4]. In a similar study, researchers examined the effects of intermittent administration of parathyroid hormone on fracture healing in ovariectomized rats [12]. After inducing bilateral tibial shaft fractures in the rat models and then stabilizing them via intramedullary nailing with Kirschner wires, the animals were given daily doses of either saline, 17-estradiol, or recombinant PTH (1–84) for 30 consecutive days. Morphometric and mechanical analyses of fracture callus were used to assess fracture healing. The results of the study showed that intermittent administration of PTH increased the morphometric and mechanical parameters of fracture callus (callus length, callus diameter, ultimate load, ultimate stiffness, ultimate stress, etc.) [12]. Intermittent administration of PTH (1–34) also seems to have a positive influence on callus formation and mechanical strength of tibial fractures in rats [6]. After daily administration of 60 g PTH (1–34), 200 g PTH (1–34), and saline solution, rats that were given daily doses of 200 g experienced increases in both external callus volume as well as ultimate axial load. Finally, a group of researchers investigated the efficacy of a parathyroid hormone related protein (PTHrP) analog as systemic therapy for impaired bone healing in corticosteroid-treated rabbits [9]. A 1mm defect was created bilaterally in the ulnae of 30 rabbits and delayed healing was induced by administering daily prednisone injections beginning 2 months prior to killing the rabbits and continuing all the way up to the time of killing. At 6 weeks postinjury, 9 out of 10 rabbits in the experimental group had achieved radiographic union and only 2 out of 10 in the control (saline) group had achieved similar results in that same time period. PTHrP was shown to be an effective therapy for preventing impaired bone healing as it caused higher radiographic intensity, larger callus area, increased stiffness, and increased torque.
patients with osteoporosis (Fig. 1). In a prospective randomized, double blind study, Aspenberg et al. compared the effects of 20 and 40 g/day teriparatide injections versus placebo on the time to radiographic healing of distal radial fractures in postmenopausal women [7]. Radiographic evidence of complete cortical bridging in three of four cortices happened earlier for patients assigned to the teriparatide 20 g/day group (7.4 weeks) when compared to patients who were assigned to the placebo group (9.1 weeks). Another study compared mean time for healing and functional outcome in two groups of elderly women who had suffered osteoporotic pelvic fractures: one group received daily 100 g parathyroid hormone (1–84) injections, while the other group received no treatment [13]. Patients who received the PTH (1–84) injections accelerated radiographic and clinical fracture healing (7.8 weeks) when compared to patients who received no treatment (12.6 weeks, p<0.001). Numerous case series state the safety and potential benefits of teriparatide use in patients recovering from fractures. One such study describes the effects of daily 20 g teriparatide injections on a cohort of 145 patients who had failed previous fracture healing, i.e. presented some form of nonunion or delayed union, or were high-risk candidates for healing acute fractures [10]. Ninety-three percent of patients demonstrated radiographic and clinical union of their fractures, and only 3% of patients failed to see early progression to clinical and radiographic union. Additional case studies have shown that delayed healing in acute and stress fractures were well treated with daily teriparatide injections along with a Vitamin/ calcium citrate supplement. Raghavan et al. showed that two women with slow healing metatarsal stress fracture healed within four weeks of starting PTH therapy [14]. Likewise, Borges et al. presents the case of an 84-year-old woman with a transtrochanteric femur fracture that showed slow progression of fracture healing one month postsurgery and healed very quickly after initiating daily 20 g doses of teriparatide [8].
Teriparatide and bone healing: clinical research
Recommendations for teriparatide usage in fracture patients
The clinical benefits of teriparatide are likely to extend beyond its approved use as a fracture prevention drug in
The decision to use teriparatide in patients with moderate or severe osteoporosis and a fracture must be considered
S38
C. Collinge and J. Favela / Injury, Int. J. Care Injured 47 S1 (2016) S36–S38
thoughtfully, as there is no cookbook answer for its use in this setting. Despite some promising results in animal studies and positive clinical support, regulatory bodies such as the U.S. Food and Drug Administration do not currently approve teriparatide for the enhancement of fracture healing. There are a few scenarios where teriparatide might be considered in patients with osteoporosis and a fracture. First, it might be considered when a patient with severe osteoporosis has been taking bisphosphonates for a number of years and has a fracture not expected to predictably unite, e.g. atypical femur fracture or open tibia fracture. Teriparatide could be used to treat the osteoporosis, while providing a vacation from bisphosphonates, and potentially providing a trophic effect on fracture healing. The drug also might be considered in cases where an osteoporotic patient has failed fracture healing and is considering surgical treatment e.g. non-union surgery. It seems prudent to reevaluate these patients frequently and reconsider which drug class of osteoporotic drug is best for the patient. Finally, it must be stressed that we do not recommend teriparatide in osteoporotic patients that may be well treated with bisphosphonates and a fracture is expected to heal uneventfully, nor when patients with metabolically normal bone have a fracture. Research shows that dosing may influence teriparatide’s anabolic effect on bone healing [5,7,10,11]; 20 g per day given subcutaneously appears beneficial for stimulating union, while a 40 g daily injection has little to no effect on the time to fracture healing. There is some controversy as to how long patients should continue to use teriparatide after their fracture has been treated. While the recommended use is for a maximum period of 2 years, it remains unclear as to whether the patient should take teriparatide only until the fracture has healed or whether he/ she should take the drug for the entire two year period. Several factors must be taken into consideration before being able to make this decision. Contraindications to teriparatide treatment include hypersensitivity to PTH, PTH (1–34), or any of the drug’s excipients. There is also a potential risk of osteosarcoma associated with the use of teriparatide; therefore patients at an increased baseline risk of osteosarcoma (Paget’s disease of bone, pediatric patients with open epiphyses, and prior external beam or implant radiation therapy involving the skeleton) should avoid this form of treatment. Teriparatide injections also pose a significant financial burden, thus the patient’s ability to manage the cost of this therapy is likely to determine how long he/she will receive this treatment. Additionally, one must carry out a thorough assessment of the patient’s response to the drug, making sure that there are no serious side effects threatening the patient’s well-being, both now and in the future. Ultimately, the decision to continue teriparatide treatment up to the recommended last page reference
2-year period is a complex one and it involves careful analysis of the patient’s entire medical history. There are currently no known alternatives to teriparatide; however, there are many ongoing studies and clinical trials testing the efficacy of new drugs that may become available in a short period of time. Conflict of interest The authors have no conflicts of interest relating to the subject matter discussed in this manuscript. They have received no support of any kind in its creation. References [1] Deal C, Gideon J. Recombinant human PTH 1-34 (Forteo): an anabolic drug for osteoporosis. Cleve Clin J Med 2003;70:585–6, 589–90, 592–4 passim. [2] http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=aae667c5-381f4f92-93df-2ed6158d07b0. Accessed Dec 20, 2014. [3] http://www.uptodate.com/contents/parathyroid-hormone-therapy-for-osteoporosis. Accessed Dec 20, 2014. [4] Manabe T, Mori S, Mashiba T, Kaji Y, Iwata K, Komatsubara S, et al. Human parathyroid hormone (1-34) accelerates natural fracture healing process in the femoral osteotomy model of cynomolgus monkeys. Bone 2007;40:1475–82. [5] Alkhiary YM, Gerstenfeld LC, Krall E, Westmore M, Sato M, Mitlak BH, Einhorn TA. Enhancement of experimental fracture-healing by systemic administration of recombinant human parathyroid hormone (PTH 1-34). J Bone Joint Surg 2005;87:731–41. [6] Andreassen TT, Ejersted C, Oxlund H. Intermittent parathyroid hormone (1-34) treatment increases callus formation and mechanical strength of healing rat fractures. J Bone Miner Res 1999;14:960–8. [7] Aspenberg P, Genant HK, Johansson T, Nino AJ, See K, Krohn K, et al. Teriparatide for acceleration of fracture repair in humans: a prospective, randomized, double-blind study of 102 postmenopausal women with distal radial fractures. J Bone Miner Res 2010;25:404–14. [8] Borges JL, Freitas A, Bilezikian JP. Accelerated fracture healing with teriparatide. Arg Bras Endocrin Metabol 2013;57:153–6. [9] Bostrom MP, Gamradt SC, Asnis P, Vickery BH, Hill E, Avnur Z, Waters RV. Parathyroid hormone-related protein analog RS-66271 is an effective therapy for impaired bone healing in rabbits on corticosteroid therapy. Bone 2000;26:437–42. [10] Bukata SV, Kaback LA, Reynolds DG, O’Keefe RJ, Rosier RN. 1-34 PTH at physiologic doses in humans shows promise as a helpful adjuvant in difficult to heal fractures: An observational cohort of 145 patients. Presented at: 55th Annual Meeting of the Orthopaedic Research Society: February 25-28 2009. Las Vegas, NV. [11] Cipriano, CA, Issack PS, Shindle L, Werner CM, Helfet DL, Lane JM, et al. Recent advances toward the clinical application of PTH (1-34) in fracture healing. HSS J 2009;5:149–53. [12] Kim HW, Jahng JS. Effect of intermittent administration of parathyroid hormone on fracture healing in ovariectomized rats. Iowa Orthop J 1999;19:71–7. [13] Peichl P, Holzer LA, Maier R, Holzer G. Parathyroid hormone 1-84 accelerates fracture-healing in pubic bones of elderly osteoporotic women. J Bone Joint Surg 2011;93:1583–7. [14] Raghavan P, Chrisofides E. Role of teriparatide in accelerating metatarsal stress fractures healing: A case series and review of literature. Clinical Med Insights Endocrinol Diabetes 2012;5:39–45.