tumor - induced osteomalacia ( tio ) is a rare paraneoplastic disease in which causative tumor ( generally of mesenchymal origin ) gives rise to an oncogenic osteomalacial syndrome , whose underlying pathogenetic mechanism is related to the tumor s production of a phosphaturic factor that reduces the renal reabsorption of phosphates and causes renal phosphate leak . the tumors are generally small , slowly growing and non - invasive .
most are localized at long bone level , but they are frequently impossible to locate and the correct diagnosis may take 5 - 7 years .
the clinical picture is characterized by non - specific symptoms , such as hyposthenia , worsening myalgia and bone pain ( mainly affecting load - bearing areas ) , and gait alterations ( anserine gait ) . until a correct diagnosis has been made patients usually undergo symptomatic treatments without success .
those patients history is characterized by numerous pathological fractures , periprothesical fractures and prothesis mobilizations .
the elective surgical treatment of tio is tumor resection , which normally leads to a complete regression of the osteomalacial syndrome .
the consequent rehabilitation treatment must consider the complexity of the clinical - functional picture of the patient , especially if a substitution megaprothesis surgery is needed .
the clinical picture is characterized by non - specific symptoms , such as hyposthenia , worsening myalgia and bone pain ( mainly affecting load - bearing areas ) , and gait alterations ( anserine gait ) . until a correct diagnosis has been made patients usually undergo symptomatic treatments without success .
those patients history is characterized by numerous pathological fractures , periprothesical fractures and prothesis mobilizations .
the elective surgical treatment of tio is tumor resection , which normally leads to a complete regression of the osteomalacial syndrome .
the consequent rehabilitation treatment must consider the complexity of the clinical - functional picture of the patient , especially if a substitution megaprothesis surgery is needed .
the clinical history of pm ( born in 1945 ) began in 2000 , when she consulted her general practitioner because of widespread costal and vertebral pain of no known traumatic cause , mainly localized in the dorso - lumbar region .
the x - ray findings were negative , and she was prescribed non - steroidal anti - inflammatory drugs treatment without receiving any benefit . the picture remained unchanged until 2003 , when bone scintigraphy revealed areas of the pathological accumulation of the radiolabeled tracer in the proximal third of the right femoral diaphysis , some costal arches and an area of bone rarefaction in the right humeral diaphysis .
further laboratory tests revealed hypocalcemia , and so the patient started pharmacological treatment with bisphosphonates , calcium and vitamin d3 for suspected advanced osteoporosis .
because of the persistence of the painful symptoms , a bone biopsy of the humeral lesion was performed ; that led to the diagnosis of a spindle cell mesenchymal tumor , morphologically arising from a glomus tumor . given the suspicion of tio , the patient underwent octreotide scintigraphy , which revealed increased tracer uptake at the level of the medio - proximal third of the right humerus . in january 2005 , she underwent a first surgical intervention that involved curettage of the lesion , an autograft from the ipsilateral tibia , and a bone biopsy , thus allowing the final diagnosis of a phosphaturic mesenchymal tumor . as a result of an accidental fall in july 2005 , the patient suffered a subcapital fracture of the right femur and a bifocal fracture of the previously treated right humeral diaphysis .
laboratory tests once again revealed hyperphosphaturic hypophosphatemia , and so she therefore underwent dual surgery involving the implantation of a bi - articular endoprosthesis cemented to the femur , an osteosynthesis of the humerus with a screwed plate and then sent to the rehabilitation department . in 2007 , worsening humeral pain associated with disease recurrence ( confirmed by means of instrumental investigations ) led to the patient being readmitted to hospital to undergo to a segmental resection of the diseased humerus and its reconstruction by means of the insertion of a cemented 8-holed plate which , soon afterwards , were replaced with a new ipsilateral tibial graft in order to provide medial reinforcement after a distal screws displacement ( figure 1a ) .
the patient s clinical condition remained stable until april 2009 when , during an outpatient follow - up examination , she complained pain in her right hip radiating to the knee and accentuated by weight bearing .
x - rays revealed loosening of the femoral stem with bone reabsorption around the cemented area . the prosthetic stem was revised and a new femoral stem was implanted ( figure 1b ) .
in march 2010 the pain in the right hip and femur reappeared and subsequent x - rays showed partial progressive subsidence of the prosthetic stem to a depth of about 2.5 cm ( figure 1c ) .
furthermore , examinations of the humerus revealed the partial mobilization of the proximal screws ( figure 1d ) . in september 2010
the patient underwent to a new revision surgery , and due to a poor cortical bone resistance a 22 cm resection from the apex of the great trochanter were executed and a large - resection modular prosthesis was implanted .
the stem was cemented and trevira mesh was used proximally to attach the extra - rotary thigh musculature in order to reconstruct the articular capsule ( figure 1e - f ) .
the postoperative course was normal and the patient started rehabilitation training as per ad hoc protocol ( table 1 ) .
the functional outcomes and efficacy of the rehabilitation program were evaluated using the following scores ( table 2 ) : range of motion , visual analogue scale , barthel s index , toronto extremity salvage score , and musculoskeletal tumor society scale . since the 1 week of permanence in the g. pini oncological orthopedic surgery the patient started distal mobilization exercises of the treated limb to prevent venous and lymphatic pooling , selective isometric exercises for maintaining the tone and trophism of the main anti - gravitational muscles ( gluteal muscles from day 3 - 4 ) , and self - mobilization and strengthening exercises of the body districts not involved in the surgery . from the 2 week , the patient has substituted a lower limb splint with a newport hip orthosis ( figure 2 ) locked in position 0. the patient and her relatives were trained in correct wearing of the support by technical staff and nurses . from day 12 ,
the by now clinically stable patient started the training for the recovery of orthostasis and short - distance transfers ( from bed to wheelchair ) with no weight bearing .
the back of the wheelchair used was fully reclined in order to avoid the patient to flex the hip .
it was necessary to make these movements for keeping the hip in position 0 , the on - bed transfer has been made on the operated limb side , with maximum assistance of the therapist in order to avoid any rotation of the lower limb . together with the re - education of postural transfers , the patient was trained in how to reach and maintain a standing position with the support of a 4-legged walking frame ( to guarantee the greatest stability ) with the treated limb just touching the floor . from the 3 week were added exercises using a 3-stage technique .
the forward movement of the limb was compensated by a sagittal oscillation of the trunk to avoid hip flexion - extension . in order to allow the patient to adequately oscillate the operated limb without flexing the hip , she was initially asked to provide contralateral support in an equine manner ( to avoid a swinging forward movement ) balanced by the counter - oscillation of the trunk on the coronal plane .
the therapeutic exercises proposed to the patient in a prone lying position had the aim of consolidating the objectives set from the 1 week and mobilizing the knee while keeping the hip extended .
in addition to guaranteeing the early recovery of walking abilities , the knee mobilization exercises had the aim of improving the tone and trophism of the femoral quadriceps and the stiffness of the ilotibial band , which , as this was the site of surgical access , was at risk of adherences that could compromise the knee movement .
on the 21 day after surgery , the patient was transferred to gaetano pini rehabilitation centre where the orthosis was gradually released ( starting on post - surgery day 30 ) until it reached 90 of flexion by means of passive and assisted active sagittal mobilization under the pain threshold .
she also performed progressive exercises of assisted active mobilization with the hip in abduction , and strengthening exercises for her right arm overloaded by the heavy use of walking aids .
the walking re - education exercises continued with the gradual replacement of the walking frame by elbow crutches : her gait showed slight abduction of the hip ( which gradually regressed ) during both the advancement and fleetingly light weight - bearing phases .
once capable of walking autonomously for albeit short distances , the patient was given functional exercises in preparation for her return home , including stairs training , re - education in the activities of daily living , and the postural movements involved in entering and leaving a car .
a few days before being discharged , she began the weaning from the orthosis and started step training exercises in water ( with the water up to her chest - 25% of her weight borne by the limb ) .
this hydrokinetic therapy gave the treated limb an important proprioceptive stimulus in terms of weight bearing without aids , but in absolute safety conditions . throughout her stay in the rehabilitation center ,
when she was discharged 60 days after surgery , she was able of walking autonomously for long distances with the aid of two elbow crutches .
she was instructed to continue the exercises at home in order to maintain and consolidate her acquired abilities . at the orthopedic follow - up examination 2 weeks after discharge
the 6-months physiatric follow - up examination showed a clear improvement in the functional outcome measures ( table 2 ) .
the tumor - induced osteomalacia is a paraneoplastic syndrome , which causes osteomalacy , causing small dimension lesions , characterized by a slow growth without any specific anatomic localization .
those lesions can lead to pathologic fractures , which , if treated without removing the neoformation or with a partial excision , may recur subsequently , along with loosening or displacement of prothesis components .
the lesions can be studied with x - rays , computed tomography , magnetic resonance imaging , concreotide tri - phasic whole - body scintigraphy and f-18 fluorodeoxyglucose positron - emission tomography .
having confirmed the nature of the lesion , treatment of a phosphaturic - secreting mesenchymal tumor is its surgical removal with broad margins by means of unconventional techniques such as a large resection and prosthetic implantation . in absence of a correct diagnosis ,
the rehabilitation treatment of patients with tio was initially based on reducing / containing the painful symptoms and asthenia , and is naturally not beneficial .
for this reason , the worsening pain and progressive loss of functional capacities can reduce the compliance with treatment and affect patient mood .
the loss of bone mass due to this type of tumor is not associated with the muscle tissue loss , but the overall balance is usually characterized by asthenia of the main anti - gravitational , stabilizing and mobilizing muscles as a result of long pre- and post - surgery periods of immobility
. the adherence of scars due to repeated revision surgeries can also give rise to articular and functional limitations ( figure 3 ) unless they are appropriately treated . the time necessary to resume everyday living activities
is longer than after conventional surgery , and requires specific techniques strictly related to the highly invasive surgery .
the requirements are : i ) special care during the first four weeks of rehabilitation and , in any case , a longer period of hospitalization that that required after a normal hip replacement procedure ( the protocol lasts of 60 days ) ; ii ) the use of specific aids ( hip orthosis and reclinable wheelchair ) and training the patient and caregivers by nurses and technical staff in how to use them ; iii ) learning specific movement techniques to get an early recovery of a standing position and making positional changes aimed at protecting the implant stability while developing the patients residual functional capacities also by means of compensatory strategies ; iv ) particular care in treating the surgical wounds , which are more extensive than those associated with traditional prosthetic implants .
the functional pictures which result are often complex for the long diagnostic - therapeutic pathway and for the highly invasive surgery needed .
the scientific research has not validated any standard rehabilitation protocol or any specific guidelines yet .
the protocol developed at the gaetano pini orthopedic institute with the collaboration of the rehabilitation and orthopedic team has demonstrated to be effective in the case above described .
 tumor - induced osteomalacia is an osteomalacic syndrome caused by a mesenchymal origin s tumor . 
 the diagnostic procedure takes time and extensive investigations because of the characteristics of these tumors usually small dimensioned , slowly growing , non - invasive and therefore hard to locate . the differential diagnosis is determined by a bone biopsy . 
 tumor s surgical removal is the treatment of choice that leads up to a complete regression of the oncogenic malacic syndrome . in the clinical course of these patients we can often see multiple episodes of pathological fractures , peri - prosthesis fractures or prosthesis mobilizations , due to the malacic picture : surgical procedures are often widely demolitive and requires mega - prosthetic implant . 
 the rehabilitative procedure used to take care of these patients , is described in the following case report and based on the collaboration between surgical and rehabilitative teams . 
 rehabilitative pathway after hip mega - prosthesis does not find references in medical literature : the outcomes analyzed in this case report demonstrate the efficacy of the rehabilitative procedure applied . 
Introduction
Clinical picture and diagnostic work-up
Case Report
Discussion
Conclusions