Introduction

Teriparatide is a synthetic polypeptide hormone that contains the 1–34 aminoacid fragment of recombinant human parathyroid hormone (PTH 1–34). It has been approved by the US Food and Drug Administration for the treatment of postmenopausal women with osteoporosis who are at high risk for sustaining a fragility fracture [1]. Daily treatments with 20 μg of PTH (1–34) resulted in dose-dependent increases in bone mineral density in the lumbar spine and femoral neck in osteoporotic female and male patients.

Its anabolic effect is given by the stimulation of the osteoblast, which causes a net increase in both cancellous and cortical bone, thus improving bone architecture. Teriparatide has different effects on trabecular and cortical bone. Because of the high degree of remodeling and apoptosis of trabecular bone osteoblasts, teriparatide has a more profound activity on trabecular as compared to cortical bone, which has a lower degree of osteoblastic apoptosis. It has been shown that teriparatide also accelerates fracture healing by improving the biomechanical properties of the fracture callus, increasing endochondral ossification and bone remodeling in animal models. This effect has been observed in several case reports [2]. The biologic process of fracture healing is complex and impacted by multiple factors. Some of them, such as the nutritional and health conditions, are patient-dependent, while others depend on the trauma experienced and stability of the fracture. Fracture healing disorders negatively affect the patient’s quality of life and result in high healthcare costs, as a second surgery is required to stabilize the fracture and stimulate bone biology. Future biotechnologies that accelerate fracture healing may be useful tools, which might also prevent the onset of these disorders [3].

Fractures are a common occurrence and have a significant impact on the quality of life for patients and considerable economic consequences for our society. Healing occurs via rapid bone regeneration followed by osteoclast-mediated remodeling resulting in new bone with structural integrity and a geometrical configuration similar to that prior to the injury. In the majority of cases, healing is uneventful, but in 5–10 % of cases delayed or impaired healing occurs [4]. Nonunion of a fracture represents the most dramatic example of poor healing as complete restoration fails in the absence of some form of treatment. Thus, the normal biologic healing process is deficient in achieving complete repair.

We define nonunion as the non-consolidation at the fracture site within 6 months. In these cases, only a change in treatment can lead to bone union. Sometimes there is no necessity to wait 6 months. This occurs when we have no progress in callus formation at fracture site at 4 weeks intervals follow-up. On the other hand, when there are indications of progress in callus formation, it is wise to wait more than 6 months [5].

Nonunion is permanent failure of healing process, and we think that in most of the cases, a second intervention will be necessary. It is a severe complication for the patient, which has a negative impact on his quality of life and, undoubtedly, which is not exempt of risks and potential complications and increases healthcare costs.

Before coming to talk about nonunion, we have a phase in which we note delays in consolidation. It is in these cases that we think need to give an additional stimulus to the repair process. Chintamaneni et al. [6] described a case of nonunion in the body of the sternum of a 67-year-old male after a motor vehicle accident who was treated with teriparatide; healing was achieved at 9 months. Rubery and Bukata [7] described a series with 3 cases of nonunions in type III odontoid fractures which, after conservative treatment with external immobilization, were successfully healed with teriparatide, with clinical improvement.

The existing basic science data suggest a role for PTH signaling in the regulation of chondrogenesis and osteogenesis. Investigations in humans have confirmed an anabolic role for PTH (1–34) in enhancing bone density and reducing fracture risk. Animal studies on fracture healing suggest that PTH signaling improves the biomechanical properties of fracture callus and accelerates callus formation, endochondral ossification, and bone remodeling. We present a case report of delayed union of a femoral fracture treated with teriparatide (rhPTH 1–34).

Case report

Caucasian 80-year-old white woman had an accident in October 2011. She was diagnosed with right distal metaphyseal femoral fracture on total knee arthroplasty (Fig. 1a, b). She underwent surgery at our center consisting of ORIF with lateral femoral locking plate in October 2011.

Fig. 1
figure 1

Right distal metaphyseal femoral fracture on total knee arthroplasty

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According to the Italian law, Ethical approval for this study was not required because it involved only routine clinical follow-up and radiographic examination. Written informed consent has been obtained from the patient. With this consent, the patient authorizes the surgical treatment and also the collection and publication of clinical data about his case for scientific and educational purposes even outside the institution.

Radiological controls at 5 and 7 months did not show any signs of healing (Fig. 2a, b). The patient was treated also with magnet therapy. This was consistent with the clinical manifestations of pain and right leg weakness. The physical examination and laboratory tests, including white blood cell counts, C-reactive protein, and erythrocyte sedimentation rate, were normal, which permitted to rule out underlying infection. The patient denied smoking, alcohol abuse and had no history of metabolic disease or glucocorticoid intake.

Fig. 2
figure 2

Postoperative X-ray after fracture fixation with lateral femoral locking plate at 7 months

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Other laboratory data, including serum alkaline phosphatase, PTH, and calcium, were normal part of a low blood level of Vitamin D.

The patient declined consented to an empiric, off-label therapy with teriparatide at approved doses for the treatment of osteoporosis (20 mg/day), as an attempt to treat the atrophic nonunion.

After 2 months of treatment with teriparatide, an X-ray showed the presence of bone bridges and a decreased gap between fragments. We also noticed the rx increased bone density in the site of fracture.

After 3 months of treatment, healing was complete, coinciding with the disappearance of pain (Fig. 3a, b). The patient recovered muscle strength in order to assume the standing position and walk without support. No side effects attributable to the drug were observed during treatment.

Fig. 3
figure 3

X-ray control at 10 months

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Conclusion

PTH (1–34) is likely to be a potent agent for enhancing fracture healing in patients with poor fracture healing potential such as those with osteoporosis, prolonged steroid use, and recalcitrant nonunions. At this point, prospective randomized clinical trials are needed to determine the safety, dosage, and efficacy of PTH (1–34) in augmenting fracture healing in humans.

We are considering the crucial role of teriparatide in our case because the fracture site of the patient showed no signs of bone healing after 7 months. The synthesis of the fracture was carried out technically correct. The problem of infection was also excluded from the clinic as well as by blood tests.

She has always used a knee brace long-armed, and the load was not granted for failure to callus formation for the first 5 months. We allow load on inferior limb after 5 months to give mechanical stimulation to the formation of callus.

Despite the grant of the load, the healing process did not start for a further 2 months. The patient was subjected to all kinds of treatment to stimulate bone healing such as the magnetotherapy and the progressive load.

Since the introduction of teriparatide in the seventh month, we had an accelerated healing process that is completed in 3–4 months. Our case report seems to confirm the effect of TPTD as bone induction through a more rapid healing of fractures. The TPTD could have a potentially important role in treating some forms of nonunion especially where bone metabolism is compromised. Thus, one could hypothesize the possibility of a medical treatment with TPTD both as a preventive and as support to the synthesis.