Osteoporos Int (2015) 26:2209–2212 DOI 10.1007/s00198-015-3191-1
CASE REPORT
Atypical femur fractures in a patient with pycnodysostosis: a case report J. Hashem 1 & R. Krochak 1 & M. D. Culbertson 1 & C. Mileto 1 & H. Goodman 1
Received: 18 April 2015 / Accepted: 27 May 2015 / Published online: 4 June 2015 # International Osteoporosis Foundation and National Osteoporosis Foundation 2015
Abstract Pycnodysostosis is a rare autosomal recessive disease due to a mutation in the gene for the enzyme Cathepsin K. It is characterized by short stature, craniofacial dysmorphias, osteosclerosis, and brittle bones. There are only a few reports in the literature describing surgical interventions for long bone fractures in pycnodysostosis patients, most of which describe intramedullary nail treatment of isolated long bone fractures. We describe a case in which a pregnant female with pycnodysostosis presented with a shaft fracture of the left femur following minor trauma and a history of increasing thigh pain. Radiographs obtained in the emergency room also revealed an impending subtrochanteric fracture of the contralateral side. The acute left femoral shaft fracture was treated with an adolescent-sized intramedullary nail; it was decided to defer surgery on the contralateral side until after pregnancy. Three months later, the patient had the contralateral femur prophylactically fixated with a plate and screws. One year after the index surgery, both methods demonstrated satisfactory healing both clinically and radiographically. Although we recommend use of an intramedullary nail for long bone fractures in patients with pycnodysostosis, a plate can be utilized if health conditions or skeletal morphology precludes use of a nail.
Keywords Atypical fractures . Cathepsin K . Intramedullary nail . Pycnodysostosis
* J. Hashem [email protected] 1
Department of Orthopaedic Surgery, Maimonides Medical Center, 927 49th Street, Brooklyn, NY 11219, USA
Introduction Pycnodysostosis is a rare autosomal recessive condition marked by distinct clinical features that include short stature, craniofacial dysmorphias, osteosclerosis, and unusually brittle bone. The abnormal skeletal morphology and bone composition in pycnodysostosis result from loss of Cathepsin K (CTSK) activity: an enzyme that degrades matrix proteins during osteoclast-mediated bone remodeling [1, 2]. Since its naming and description by Maroteaux and Lamy in 1962, less than 200 cases have been reported [1, 3]. Few reports detail surgical interventions for long bone fractures in pycnodysostotic patients [4–9]. We describe the case of a pregnant female with pycnodysostosis who sustained an atypical femoral shaft fracture with an impending subtrochanteric fracture in the contralateral femur.
Case report A 36-year-old female presented to the emergency room 29 weeks gravid and unable to ambulate following minor trauma to the left thigh preceded by a 1-month history of increasing thigh pain. She was diagnosed with pycnodysostosis in early adolescence and had a history of lower limb stress fractures treated with long-term casting. There was no family history of similar bone diseases. Examination revealed craniofacial abnormalities, micrognathia, short broad hands, and small stature (139.7 cm). The abdomen was normal for her gestational stage. Her left lower extremity was shortened and externally rotated, and she exhibited tenderness on palpation of the left thigh. The skin was intact, and her neurovascular exam was normal. Radiographs revealed a transverse femoral shaft fracture with lateral beaking and thickened cortices. The contralateral femur also showed signs of cortical thickening and lateral
2210
beaking, raising concern for an impending fracture (Fig. 1). Delaying surgery until after birth was ruled out after obstetric consultation. The patient was consented for open reduction and internal fixation of the left femur with an intramedullary (IM) nail. The patient was placed supine on a fracture table. She was initially given spinal anesthesia, but later administered general anesthesia. An adolescent-sized, trochanteric-entry IM nail was selected and templated due to the patient’s short stature and narrowed canal. The trochanter was entered with a guide wire and opening reamer. It was immediately apparent that the patient had extremely sclerotic bone. Entering the canal proved problematic, and the isthmus could not be breached despite the use of guide wires and both cannulated powered and hand reamers. The fracture site was therefore exposed via a lateral approach and the fracture ends delivered into the wound. The canal was opened with a high-speed burr, and a retrograde guide wire was placed. The canal was then enlarged with a power reamer.
Fig. 1 Preoperative radiographs in pycnodysostosis patient. a A-P of the right femur showing thickened cortices and lateral beaking (white arrow) suggestive of impending fracture. b A-P of the left femur showing acute transverse fracture of the femoral shaft. c Lateral view of the right tibia revealing evidence of healed stress fractures (white arrow). d Lateral cranial film showing thickening at the base of the skull (black dart), frontal bossing (white dart), and obtuse mandibular angle (white arrow) often observed in pycnodysostosis
Osteoporos Int (2015) 26:2209–2212
Trajectory and removal of the correct bone volume were verified fluoroscopically. This procedure was repeated in the anterograde direction for the distal fragment. The fracture was reduced over a long, beaded-tip guide wire, and the canal opened via flexible reamers to a final diameter of 10 mm. An 8.2 mm by 280 mm adolescent-sized, lateral-entry nail (Synthes, West Chester, PA) was placed over the guide wire and locked using two proximal screws and two distal screws. At this time, the contralateral femur was imaged, confirming the atypical appearance of the bone. Prophylactic fixation was considered, but deemed inappropriate given the pregnancy. The patient left the operating room in stable condition. Post-operatively, the patient was directed to bear weight, as tolerated, with the use of a walker and started on a course of enoxaparin to prevent deep venous thrombosis until she gave birth. Four weeks after surgery, the patient presented with persistent drainage from the proximal incision, erythema, and a 2-cm dehiscence. Ultrasound revealed a collection extending to the fascia. The incision was partially opened and a 10-mL sample of seropurulent fluid collected for cultures. The patient was then started on oral antibiotics. The possibility of a deep infection was considered, but it was decided that revision or extensive debridement should be postponed until after the baby was born. Despite antibiotics, the patient experienced worsening pain and drainage. She returned to the Emergency Department later that same week for irrigation and debridement. The wound was packed, and she was given intravenous antibiotics. Cultures revealed methicillin-resistant Staphylococcus aureus (MRSA) in the wound. The patient was discharged after her condition improved and returned for weekly follow-up visits. After an initial aspiration of 40 mL of seropurulent fluid during the first follow-up, no further drainage was noted and the patient went on to heal. The patient gave birth 2 months after surgery and was evaluated 2 weeks after that. Her incisions were well-healed with no sign of fluctuance. She complained of pain in her ankles; bilateral tibia/fibula radiographs revealed anterior cortical thickening consistent with old stress fractures. X-rays showed callus development, though it was less extensive than normal. Atypical remodeling was anticipated, however, as her condition is associated with osteoclast dysfunction. Three months after surgery, the patient reported less pain in the left thigh, but worsening right thigh pain. X-rays of the right femur confirmed the persistence of the atypical subtrochanteric beaking. Prophylactic fixation was discussed with the patient, but at that time, she opted against surgery. Approximately 1 week later, she returned after a fall left her with more severe pain in the right thigh. X-rays did not show further damage to the femur. The patient then opted for prophylactic fixation. Due to the difficulty with the initial intramedullary fixation, the second surgery was planned as a plate fixation under combined spinal and epidural anesthesia. Lateral beaking was evident upon exposure of the site. A plate was placed with a
Osteoporos Int (2015) 26:2209–2212
combination of locked and non-locking screws. The immediate post-operative course was uneventful. One month post-operatively, the patient was doing well and reported less pain than she had prior to surgery. There were no signs of infection at either surgical site. Implants in both femurs were properly positioned with some sign of callus in the left femur. One year after the index surgery, the patient was ambulating with minimal pain, manifesting as occasional bouts of bilateral pain in the tibiae. Radiographs showed that the plated right femur had healed and that the left femur exhibited significant bridging callous across the fracture (Fig. 2).
Discussion Various methods of femoral fracture repair have been employed in pycnodysostotic patients including IM nails, external fixation, and, less frequently, plate fixation [4–9]. Kundu et al. proposed that IM nails should be used to increase the chance of union and decrease infection risks [7]. Another report following a patient with multiple fragility fractures due to pycnodysostosis over 27 years similarly recommended IM nail fixation [6]. Several reports describe difficulty placing IM nails due to sclerosis and medullary canal constriction [5–8]. Kundu et al. indicated good function and healing 2 years after IM nail fixation, but found that sclerosis complicated hardware placement [7]. Similar difficulties were encountered in this case; plate fixation was elected for the impending fracture in the Fig. 2 Radiographs showing the left femur exhibiting significant bridging callous across the fracture and the plated right femur that has healed. Note that oper. indicates intraoperative fluoroscopic imaging
2211
contralateral femur since the pathologic bone impeded the initial IM nail placement. Plate fixation for lower limb fractures has yielded conflicting reports. One case described a pycnodysostotic patient with broken plates and pseudoarthroses in both tibiae; another found incomplete healing and pain 4 months after plate fixation of an atypical subtrochanteric femur fracture [10, 4]. However, other groups achieved tibial union 1 year postoperatively using bone grafts and compression plating and healing over a normal timeframe after plating a transverse femur fracture [11, 9]. Remodeled bone in pycnodysostotic patients lacks both cellularity and quantity. Microscopically, lamellar bone lacks structural organization and exhibits large inclusions of mineralized cartilage; histologic examination also reveals sclerotic trabeculae. Lamellar collagen fibrils are highly disorganized, consistent with the Cathepsin K dysfunction that yields faulty bone remodeling and altered mechanical properties [11, 12]. However, healing is often sufficient to restore function. Callus formation and union occur, albeit more slowly than normal [6, 5, 10]. Interestingly, the hallmark osteoclast dysfunction in this patient yielded cortical thickening and lateral beaking reminiscent of fracture patterns described in long-term bisphosphonate users [13, 14]. Clinically, pycnodysostosis resembles osteopetrosis, in that both exhibit low bone turnover, and sclerotic bone and neither can currently be treated effectively. However, osteopetrosis, which is actually a set of related maladies caused by mutations in genes controlling osteoclast function, is etiologically distinct from pycnodysostosis [11, 15]. While some forms of osteopetrosis are associated with increased osteomyelitis and
2212
Osteoporos Int (2015) 26:2209–2212 4.
bone marrow suppression, pycnodysostotic patients do not typically suffer from these complications [16]. Although our patient developed a surgical site infection, this cannot be specifically attributed to her metabolic bone disease. In most circumstances, the protection conferred by IM nails constitutes the best fixation for pycnodysostotic patients. In this case, both an IM nail and a contralateral plate were employed for bilateral fractures. After 1 year, the patient exhibited good healing in both femurs and excellent range of motion in the hips and knees. In patients with highly aberrant canal anatomy or stressors such as pregnancy, protracted surgical times required for an IM nailing may increase complication risks. It is thus advisable that surgeons be prepared to execute alternative fixation techniques such as external fixation or plating prior to surgery. Thorough follow-up is also recommended for early detection of any potential complications.
11.
Conflicts of interest None
12.
References
13.
1.
2.
3.
Xue Y, Cai T, Shi S, Wang W, Zhang Y, Mao T et al (2011) Clinical and animal research findings in pycnodysostosis and gene mutations of cathepsin K from 1996 to 2011. Orphanet J Rare Dis 6(1): 20 Gelb BD, Moissoglu K, Zhang J, Martignetti JA (1996) Cathepsin K: isolation and characterization of the murine cDNA and genomic sequence, the homologue of the human pycnodysostosis gene. Biochem Mol Med 59(2):200–206 Naeem M, Sheikh S, Ahmad W (2009) A mutation in CTSK gene in an autosomal recessive pycnodysostosis family of Pakistani origin. BMC Med Genet 10(1):76
5.
6. 7.
8.
9.
10.
14.
15.
16.
Yates CJ, Bartlett MJ, Ebeling PR (2011) An atypical subtrochanteric femoral fracture from pycnodysostosis: a lesson from nature. J Bone Miner Res 26(6):1377–1379 Nakase T, Yasui N, Hiroshima K, Ohzono K, Higuchi C, Shimizu N et al (2006) Surgical outcomes after treatment of fractures in femur and tibia in pycnodysostosis. Arch Orthop Trauma Surg 127(3): 161–165 Bor N, Rubin G, Rozen N (2011) Fracture management in pycnodysostosis. J Pediatr Orthop B 20(2):97–101 Kundu ZS, Marya KM, Devgan A, Yadav V, Rohilla S (2004) Subtrochanteric fracture managed by intramedullary nail in a patient with pycnodysostosis. Joint Bone Spine 71(2):154–156 Roth VG (1976) Pycnodysostosis presenting with bilateral subtrachanteric fractures: case report. Clin Orthop Relat Res 117: 247–253 Lyritis G, Rapidis A, Dimitracopoulos B (1982) Orthopaedic problems in patients with pycnodysostosis. Prog Clin Biol Res 104:199– 204 Emami-Ahari Z, Zarabi M, Javid B (1969) Pycnodysostosis. J Bone Joint Surg- Bri Vol 51(2):307–312 Meredith SC, Simon MA, Laros GS, Jackson MA (1978) Pycnodysostosis. A clinical, pathological, and ultramicroscopic study of a case. J Bone Joint Surg Am 60(8):1122–1127 Fratzl-Zelman N, Valenta A, Roschger P, Nader A, Gelb BD, Fratzl P et al (2004) Decreased bone turnover and deterioration of bone structure in two cases of pycnodysostosis. J Clin Endocrinol Metab 89(4):1538–1547 Lenart BA, Lorich DG, Lane JM (2008) Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med 358(12):1304–1306 Goh S-K, Yang KY, Koh JSB, Wong MK, Chua SY, Chua DTC et al (2007) Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg-BriVol 89(3): 349–353 Chavassieux P, Seeman E, Delmas PD (2007) Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease. Endocr Rev 28(2):151–164 Stark Z, Savarirayan R (2009) Osteopetrosis. Orphanet J Rare Dis 4:5
CASE REPORT
Atypical femur fractures in a patient with pycnodysostosis: a case report J. Hashem 1 & R. Krochak 1 & M. D. Culbertson 1 & C. Mileto 1 & H. Goodman 1
Received: 18 April 2015 / Accepted: 27 May 2015 / Published online: 4 June 2015 # International Osteoporosis Foundation and National Osteoporosis Foundation 2015
Abstract Pycnodysostosis is a rare autosomal recessive disease due to a mutation in the gene for the enzyme Cathepsin K. It is characterized by short stature, craniofacial dysmorphias, osteosclerosis, and brittle bones. There are only a few reports in the literature describing surgical interventions for long bone fractures in pycnodysostosis patients, most of which describe intramedullary nail treatment of isolated long bone fractures. We describe a case in which a pregnant female with pycnodysostosis presented with a shaft fracture of the left femur following minor trauma and a history of increasing thigh pain. Radiographs obtained in the emergency room also revealed an impending subtrochanteric fracture of the contralateral side. The acute left femoral shaft fracture was treated with an adolescent-sized intramedullary nail; it was decided to defer surgery on the contralateral side until after pregnancy. Three months later, the patient had the contralateral femur prophylactically fixated with a plate and screws. One year after the index surgery, both methods demonstrated satisfactory healing both clinically and radiographically. Although we recommend use of an intramedullary nail for long bone fractures in patients with pycnodysostosis, a plate can be utilized if health conditions or skeletal morphology precludes use of a nail.
Keywords Atypical fractures . Cathepsin K . Intramedullary nail . Pycnodysostosis
* J. Hashem [email protected] 1
Department of Orthopaedic Surgery, Maimonides Medical Center, 927 49th Street, Brooklyn, NY 11219, USA
Introduction Pycnodysostosis is a rare autosomal recessive condition marked by distinct clinical features that include short stature, craniofacial dysmorphias, osteosclerosis, and unusually brittle bone. The abnormal skeletal morphology and bone composition in pycnodysostosis result from loss of Cathepsin K (CTSK) activity: an enzyme that degrades matrix proteins during osteoclast-mediated bone remodeling [1, 2]. Since its naming and description by Maroteaux and Lamy in 1962, less than 200 cases have been reported [1, 3]. Few reports detail surgical interventions for long bone fractures in pycnodysostotic patients [4–9]. We describe the case of a pregnant female with pycnodysostosis who sustained an atypical femoral shaft fracture with an impending subtrochanteric fracture in the contralateral femur.
Case report A 36-year-old female presented to the emergency room 29 weeks gravid and unable to ambulate following minor trauma to the left thigh preceded by a 1-month history of increasing thigh pain. She was diagnosed with pycnodysostosis in early adolescence and had a history of lower limb stress fractures treated with long-term casting. There was no family history of similar bone diseases. Examination revealed craniofacial abnormalities, micrognathia, short broad hands, and small stature (139.7 cm). The abdomen was normal for her gestational stage. Her left lower extremity was shortened and externally rotated, and she exhibited tenderness on palpation of the left thigh. The skin was intact, and her neurovascular exam was normal. Radiographs revealed a transverse femoral shaft fracture with lateral beaking and thickened cortices. The contralateral femur also showed signs of cortical thickening and lateral
2210
beaking, raising concern for an impending fracture (Fig. 1). Delaying surgery until after birth was ruled out after obstetric consultation. The patient was consented for open reduction and internal fixation of the left femur with an intramedullary (IM) nail. The patient was placed supine on a fracture table. She was initially given spinal anesthesia, but later administered general anesthesia. An adolescent-sized, trochanteric-entry IM nail was selected and templated due to the patient’s short stature and narrowed canal. The trochanter was entered with a guide wire and opening reamer. It was immediately apparent that the patient had extremely sclerotic bone. Entering the canal proved problematic, and the isthmus could not be breached despite the use of guide wires and both cannulated powered and hand reamers. The fracture site was therefore exposed via a lateral approach and the fracture ends delivered into the wound. The canal was opened with a high-speed burr, and a retrograde guide wire was placed. The canal was then enlarged with a power reamer.
Fig. 1 Preoperative radiographs in pycnodysostosis patient. a A-P of the right femur showing thickened cortices and lateral beaking (white arrow) suggestive of impending fracture. b A-P of the left femur showing acute transverse fracture of the femoral shaft. c Lateral view of the right tibia revealing evidence of healed stress fractures (white arrow). d Lateral cranial film showing thickening at the base of the skull (black dart), frontal bossing (white dart), and obtuse mandibular angle (white arrow) often observed in pycnodysostosis
Osteoporos Int (2015) 26:2209–2212
Trajectory and removal of the correct bone volume were verified fluoroscopically. This procedure was repeated in the anterograde direction for the distal fragment. The fracture was reduced over a long, beaded-tip guide wire, and the canal opened via flexible reamers to a final diameter of 10 mm. An 8.2 mm by 280 mm adolescent-sized, lateral-entry nail (Synthes, West Chester, PA) was placed over the guide wire and locked using two proximal screws and two distal screws. At this time, the contralateral femur was imaged, confirming the atypical appearance of the bone. Prophylactic fixation was considered, but deemed inappropriate given the pregnancy. The patient left the operating room in stable condition. Post-operatively, the patient was directed to bear weight, as tolerated, with the use of a walker and started on a course of enoxaparin to prevent deep venous thrombosis until she gave birth. Four weeks after surgery, the patient presented with persistent drainage from the proximal incision, erythema, and a 2-cm dehiscence. Ultrasound revealed a collection extending to the fascia. The incision was partially opened and a 10-mL sample of seropurulent fluid collected for cultures. The patient was then started on oral antibiotics. The possibility of a deep infection was considered, but it was decided that revision or extensive debridement should be postponed until after the baby was born. Despite antibiotics, the patient experienced worsening pain and drainage. She returned to the Emergency Department later that same week for irrigation and debridement. The wound was packed, and she was given intravenous antibiotics. Cultures revealed methicillin-resistant Staphylococcus aureus (MRSA) in the wound. The patient was discharged after her condition improved and returned for weekly follow-up visits. After an initial aspiration of 40 mL of seropurulent fluid during the first follow-up, no further drainage was noted and the patient went on to heal. The patient gave birth 2 months after surgery and was evaluated 2 weeks after that. Her incisions were well-healed with no sign of fluctuance. She complained of pain in her ankles; bilateral tibia/fibula radiographs revealed anterior cortical thickening consistent with old stress fractures. X-rays showed callus development, though it was less extensive than normal. Atypical remodeling was anticipated, however, as her condition is associated with osteoclast dysfunction. Three months after surgery, the patient reported less pain in the left thigh, but worsening right thigh pain. X-rays of the right femur confirmed the persistence of the atypical subtrochanteric beaking. Prophylactic fixation was discussed with the patient, but at that time, she opted against surgery. Approximately 1 week later, she returned after a fall left her with more severe pain in the right thigh. X-rays did not show further damage to the femur. The patient then opted for prophylactic fixation. Due to the difficulty with the initial intramedullary fixation, the second surgery was planned as a plate fixation under combined spinal and epidural anesthesia. Lateral beaking was evident upon exposure of the site. A plate was placed with a
Osteoporos Int (2015) 26:2209–2212
combination of locked and non-locking screws. The immediate post-operative course was uneventful. One month post-operatively, the patient was doing well and reported less pain than she had prior to surgery. There were no signs of infection at either surgical site. Implants in both femurs were properly positioned with some sign of callus in the left femur. One year after the index surgery, the patient was ambulating with minimal pain, manifesting as occasional bouts of bilateral pain in the tibiae. Radiographs showed that the plated right femur had healed and that the left femur exhibited significant bridging callous across the fracture (Fig. 2).
Discussion Various methods of femoral fracture repair have been employed in pycnodysostotic patients including IM nails, external fixation, and, less frequently, plate fixation [4–9]. Kundu et al. proposed that IM nails should be used to increase the chance of union and decrease infection risks [7]. Another report following a patient with multiple fragility fractures due to pycnodysostosis over 27 years similarly recommended IM nail fixation [6]. Several reports describe difficulty placing IM nails due to sclerosis and medullary canal constriction [5–8]. Kundu et al. indicated good function and healing 2 years after IM nail fixation, but found that sclerosis complicated hardware placement [7]. Similar difficulties were encountered in this case; plate fixation was elected for the impending fracture in the Fig. 2 Radiographs showing the left femur exhibiting significant bridging callous across the fracture and the plated right femur that has healed. Note that oper. indicates intraoperative fluoroscopic imaging
2211
contralateral femur since the pathologic bone impeded the initial IM nail placement. Plate fixation for lower limb fractures has yielded conflicting reports. One case described a pycnodysostotic patient with broken plates and pseudoarthroses in both tibiae; another found incomplete healing and pain 4 months after plate fixation of an atypical subtrochanteric femur fracture [10, 4]. However, other groups achieved tibial union 1 year postoperatively using bone grafts and compression plating and healing over a normal timeframe after plating a transverse femur fracture [11, 9]. Remodeled bone in pycnodysostotic patients lacks both cellularity and quantity. Microscopically, lamellar bone lacks structural organization and exhibits large inclusions of mineralized cartilage; histologic examination also reveals sclerotic trabeculae. Lamellar collagen fibrils are highly disorganized, consistent with the Cathepsin K dysfunction that yields faulty bone remodeling and altered mechanical properties [11, 12]. However, healing is often sufficient to restore function. Callus formation and union occur, albeit more slowly than normal [6, 5, 10]. Interestingly, the hallmark osteoclast dysfunction in this patient yielded cortical thickening and lateral beaking reminiscent of fracture patterns described in long-term bisphosphonate users [13, 14]. Clinically, pycnodysostosis resembles osteopetrosis, in that both exhibit low bone turnover, and sclerotic bone and neither can currently be treated effectively. However, osteopetrosis, which is actually a set of related maladies caused by mutations in genes controlling osteoclast function, is etiologically distinct from pycnodysostosis [11, 15]. While some forms of osteopetrosis are associated with increased osteomyelitis and
2212
Osteoporos Int (2015) 26:2209–2212 4.
bone marrow suppression, pycnodysostotic patients do not typically suffer from these complications [16]. Although our patient developed a surgical site infection, this cannot be specifically attributed to her metabolic bone disease. In most circumstances, the protection conferred by IM nails constitutes the best fixation for pycnodysostotic patients. In this case, both an IM nail and a contralateral plate were employed for bilateral fractures. After 1 year, the patient exhibited good healing in both femurs and excellent range of motion in the hips and knees. In patients with highly aberrant canal anatomy or stressors such as pregnancy, protracted surgical times required for an IM nailing may increase complication risks. It is thus advisable that surgeons be prepared to execute alternative fixation techniques such as external fixation or plating prior to surgery. Thorough follow-up is also recommended for early detection of any potential complications.
11.
Conflicts of interest None
12.
References
13.
1.
2.
3.
Xue Y, Cai T, Shi S, Wang W, Zhang Y, Mao T et al (2011) Clinical and animal research findings in pycnodysostosis and gene mutations of cathepsin K from 1996 to 2011. Orphanet J Rare Dis 6(1): 20 Gelb BD, Moissoglu K, Zhang J, Martignetti JA (1996) Cathepsin K: isolation and characterization of the murine cDNA and genomic sequence, the homologue of the human pycnodysostosis gene. Biochem Mol Med 59(2):200–206 Naeem M, Sheikh S, Ahmad W (2009) A mutation in CTSK gene in an autosomal recessive pycnodysostosis family of Pakistani origin. BMC Med Genet 10(1):76
5.
6. 7.
8.
9.
10.
14.
15.
16.
Yates CJ, Bartlett MJ, Ebeling PR (2011) An atypical subtrochanteric femoral fracture from pycnodysostosis: a lesson from nature. J Bone Miner Res 26(6):1377–1379 Nakase T, Yasui N, Hiroshima K, Ohzono K, Higuchi C, Shimizu N et al (2006) Surgical outcomes after treatment of fractures in femur and tibia in pycnodysostosis. Arch Orthop Trauma Surg 127(3): 161–165 Bor N, Rubin G, Rozen N (2011) Fracture management in pycnodysostosis. J Pediatr Orthop B 20(2):97–101 Kundu ZS, Marya KM, Devgan A, Yadav V, Rohilla S (2004) Subtrochanteric fracture managed by intramedullary nail in a patient with pycnodysostosis. Joint Bone Spine 71(2):154–156 Roth VG (1976) Pycnodysostosis presenting with bilateral subtrachanteric fractures: case report. Clin Orthop Relat Res 117: 247–253 Lyritis G, Rapidis A, Dimitracopoulos B (1982) Orthopaedic problems in patients with pycnodysostosis. Prog Clin Biol Res 104:199– 204 Emami-Ahari Z, Zarabi M, Javid B (1969) Pycnodysostosis. J Bone Joint Surg- Bri Vol 51(2):307–312 Meredith SC, Simon MA, Laros GS, Jackson MA (1978) Pycnodysostosis. A clinical, pathological, and ultramicroscopic study of a case. J Bone Joint Surg Am 60(8):1122–1127 Fratzl-Zelman N, Valenta A, Roschger P, Nader A, Gelb BD, Fratzl P et al (2004) Decreased bone turnover and deterioration of bone structure in two cases of pycnodysostosis. J Clin Endocrinol Metab 89(4):1538–1547 Lenart BA, Lorich DG, Lane JM (2008) Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med 358(12):1304–1306 Goh S-K, Yang KY, Koh JSB, Wong MK, Chua SY, Chua DTC et al (2007) Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg-BriVol 89(3): 349–353 Chavassieux P, Seeman E, Delmas PD (2007) Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease. Endocr Rev 28(2):151–164 Stark Z, Savarirayan R (2009) Osteopetrosis. Orphanet J Rare Dis 4:5
