Transient osteoporosis of pregnancy (TOP) is an uncommon diagnosis for acute hip pain, which can be found in young healthy women who are progressing through an otherwise normal pregnancy. The pathology and risk factors for TOP are poorly understood, and the diagnosis may be elusive with initially normal radiographs. The emergence of Magnetic Resonance (MR) has enhanced our abilities to identify signs consistent with that of TOP, but once recognized, there still remains a lack of literature on treatments to best care for both mother and fetus (1). Because of its overlap with other pathologies in terms of clinical presentation and diagnostic findings, health care providers must have a high index of suspicion for TOP when assessing acute hip pain in the pregnant patient.
A 27-year-old G5P3013 female presented with acute left hip pain during the 23rd week pregnancy. Deep posterolateral hip pain began a month prior and had worsened rapidly over several weeks. The pain was described as a constant dull ache at rest, which became increasingly sharp in nature with ambulation, pressure, and resisted abduction. Minimal relief was provided by acetaminophen, a 5-d steroid dose pack (previously prescribed by her primary care provider), heat, ice, and rest (ibuprofen was not utilized due to pregnancy). The patient denied a history of trauma to the hip or leg; however, she has had nonspecific hip pain in the past.
On examination, the patient exhibited an antalgic gait without lower limb asymmetry, atrophy, soft tissue swelling, nor gross deformity. Moderate tenderness to palpation over the left greater trochanter and lateral tendinous portion of the piriformis was present. Strength testing revealed 5/5 strength with hip flexion, extension, abduction, and adduction. Reproducible moderate pain was present on hip flexion, adduction, and internal rotation. Crepitus was not appreciated and other provocative tests (log roll, single leg raise leg, Ober's test, and FABER/FADIR) were negative. Comparatively, the right hip was without tenderness or strength deficits.
Trochanteric bursitis with piriformis strain was diagnosed based on history and physical examination, and a left trochanteric bursa injection (2 mL of 0.25% Marcaine, 2 mL of 0.1% Lidocaine, and 1 mL of Celestone) was performed. The patient was instructed to use acetaminophen as needed for pain and was educated on how to perform rehabilitative stretches and exercises.
Five days later, the patient reported a marked increase in pain with radiation down the left leg and difficulty in ambulation. With magnetic resonance imaging (MRI) not being immediately available, X-rays of the hip (with an abdominal shield to protect the fetus) were obtained to expedite further evaluation of the hip. Radiographs were read as being without acute pathology despite the worsening clinical picture prompting an MRI to be obtained.
Ten days from the initial visit, the patient scheduled an urgent appointment for very sharp left hip pain while ambulating and a dull ache at rest. The pain was 7/10 at its worst and was located deep to the left inguinal region, proximal posterior thigh, and lateral hip. Acetaminophen no longer relieved any of the pain, and the corticosteroids had been ineffective. A cane was obtained 2 d prior, which provided some relief of pain with ambulation. On physical examination, the patient had a difficult time bringing her left leg onto the examination table because of the hip pain.
Tenderness was palpated at the left anterior and lateral hip. Severe pain was present with passive range of motion to 90 degrees of flexion, 10 degrees of internal rotation, and 20 degrees of external rotation. Raising the leg off the table caused severe pain of the left hip. Gross sensation to the lower extremity was intact with 2+ dorsalis pedis and posterior tibial pulses. Her calves were nontender and without any lower extremity edema nor inguinal adenopathy. The MRI of her left hip demonstrated bone marrow edema in the femoral head, neck, and intertrochanteric region without occult fracture or femoral head collapse (Fig. 1).
Transient osteoporosis, pending stress fracture, and early avascular necrosis (AVN) were highest on the differential. Without an indication for surgery, the patient remained in the care of nonoperative specialists. Management at this time involved patient education on transient osteoporosis of the hip (TOH) and its benign, self-limited natural history. Crutches were given to the patient, and she was advised to put no more than 10% of her body weight on the left leg. In contrast to making the patient nonweight bearing, allowing for toe touch weight bearing was considered to help with ambulation and is consistent with a previous meta-analysis, which suggested that there is little difference in partial versus nonweight bearing in the progression of AVN (2). The patient also was advised to avoid rotation on a fixed foot because of the susceptibility of sustaining a fracture. The use of a wheelchair was reserved for later in the pregnancy when the patient's fall risk would increase because of her small body habitus and advanced pregnancy state, making it more difficult to support her weight with crutch walking. At work, the patient was limited to light duty/desk work.
Three weeks after the initial presentation, the left hip was worsening despite weight bearing restrictions and activity modification. Additionally, over the past couple of days, she had experienced intermittent numbness in the left calf and foot, foot swelling, and a “cold” sensation when her foot was numb. The symptoms were improved with a hot shower and positional changes. The decision was made to repeat an MRI and to obtain a left lower extremity Doppler ultrasound to evaluate for deep vein thrombosis (DVT) because of the progression of symptoms.
Ultrasound imaging showed no DVT, while the MRI demonstrated findings in the left femoral head, suggesting small early subchondral fracture versus mild AVN of the left hip with associated left femoral marrow edema. The findings were slightly less prominent as compared with the prior study, and there was no evidence of femoral head collapse (Fig. 2). These repeat findings continued to be consistent with transient osteoporosis of the left femoral head and neck, and the recommendations for treatment remained unchanged. A later diagnosis of concomitant left lumbar radiculopathy explained the patient's paresthesias to be unrelated to the patient's hip pathology.
Five weeks after the initial presentation, the patient had become increasingly frustrated because she was now bed bound, and her use of crutches had caused pain in the right hip along the adductor tendon in the right groin. The patient requested information about the use of several drugs, including deflazacort, alendronate, and calcitonin for additional treatment. The patient was not a candidate for deflazacort because it is contraindicated during the second and third trimesters of pregnancy due to crossing the placenta. Alendronate and calcitonin are category C for pregnancy and would need to be closely managed by the patient's obstetrician. The risk and benefits of starting a pregnancy category C medication was discussed with the patient versus continuing with symptomatic treatment while allowing the self-limited course of TOP to proceed. Our patient was educated on the knowledge of bisphosphonates crossing the placental barrier, although there were no reports of congenital abnormalities or growth defects (3). Because of the severity of her symptoms, it was decided along with the consultation and guidance of the patient's obstetrician to begin alendronate weekly.
One month after the initiation of alendronate, the patient went from being bed bound to returning to work without limitations. She had complete resolution of her hip pain and was ambulating normally without assistance. The patient delivered approximately 3 wk following the resolution of symptoms without complications.
TOP is a rare pathology that can occur in young healthy women in the midst of a normal pregnancy. For the pregnant mother, this may cause severe pain and fractures both before and during delivery which may require surgical intervention. TOP most commonly occurs in the second and third trimesters of pregnancy with degeneration of the femur (TOH) being most often affected. TOH is characterized by the onset of nontraumatic hip pain, which progresses in severity within weeks resulting in decreased hip range of motion, painful ambulation, and immobilization. TOP is a self-limited pathology with symptoms fully resolving after the birth of the child within 6 to 12 months (1,4–8).
The pathophysiology and specific risk factors for TOH are poorly understood. TOH is thought to have three stages. The first stage consists of several weeks of progressive hip pain with development of an antalgic gait without radiographic changes, although MRI may show edema. In the second stage, symptoms continue to worsen with radiographs now showing bone demineralization consistent with osteoporosis and normal joint spaces. Dual-energy X-ray absorptiometry scans will show a decrease in bone density, and MRI will demonstrate focal edema. After the birth of the child, the third stage consists of a gradual resolution of symptoms and radiographic changes over a 6- to 12-month period (1,4,7). The etiology of TOP is unclear with postulated theories of TOP being a result of an early state of AVN, increased osteoclast activation, viral infection, neurovascular injury, transient ischemic insult to bone, microvascular injury, hormonal imbalance, trauma, or subchondral fracture of the femoral head (1,4,7). The most common risk factor for TOH is pregnancy with others, including poor nutrition and a low calcium diet, trauma, alcohol consumption, smoking, drug use, corticosteroid use, vascular insult, inflammation, osteogenesis imperfecta, hypothyroidism, hypophosphatemia, low testosterone, or low vitamin D. There also have been cases of recurrent TOP in subsequent pregnancies (4,7).
A diagnosis of TOH is usually made when conservative treatment of the painful hip has failed, and the decision is made to pursue imaging. Conventional radiography and computed tomography (CT) are often unremarkable and show only subtle changes if there is no fracture present (9). CT may show reduced bone density of the affected area (10). Bone scintigraphy scans show increased uptake of radiotracer; however, this finding is nonspecific and may result from inflammatory changes associated with infection, AVN, or tumors (11).
MRI is the most useful imaging modality in TOH and will show findings consistent with bone marrow edema, such as low signal intensity of the marrow on T1-weighted sequences and high signal intensity on T2-weighted and fat-suppressed sequences.
This edema typically involves the subchondral bone of the femoral head and often extends to the neck of the femur and intertrochanteric region (12). Bone marrow edema is in itself a nonspecific finding, which can be seen with TOH, subchondral stress fractures, or AVN. Because AVN requires emergent intervention, studies have looked for MR patterns that can differentiate TOH from early AVN. One study showed that lack of subchondral changes on T2-weighted or contrast-enhanced T1-weighted images yielded a 100% positive predictive value for identifying transient lesions presenting with bone marrow edema (13). When considering choices for imaging during pregnancy, radiographs, CT, and bone scintigraphy are typically withheld because of the concerns of fetal exposure to ionizing radiation. MRI is the imaging of choice in pregnancy because it avoids ionizing radiation, although MRI has not conclusively been proven to be without harm to the fetus, thus it should be ordered judiciously (1,12).
When making the diagnosis of TOH, one must consider the overlap in clinical and diagnostic presentation TOH has with other pathologies. The relationship between TOH and subchondral stress fractures has been debated because there have been reported cases of TOH with and without the coexistence of subchondral stress fractures. It is unclear if one begets the other, although the existence of cases of TOH without stress fractures would tend to point to stress fractures being a consequence of TOH. Additional support for this theory comes from the weakening and demineralization of bone that occurs with the transient edema of TOH. This inadequate bone structure is likely unable to keep up normal stresses placed on the bone (14). The differentiation between AVN — a surgical emergency, and TOH, a self-limited pathology that does not progress to collapse of the femoral head or future arthritis, through careful evaluation of MRI, can prevent unnecessary surgical intervention (15). Regional migratory osteoporosis (RMO) is diagnosed when transient osteoporosis affects other joints, most commonly the contralateral. Similar to TOH, RMO follows a benign self-limited course (16).
With only a small number of published cases of TOP, treatment guidelines are not well established, although conservative therapy has primarily been documented in the literature. An approach focused on reduction of weight-bearing activities, resting the joint, and the use of anti-inflammatory drugs to reduce pain is thought to take advantage of the naturally self-limited course of TOP (17). Any further interventions in the treatment of TOP should be discussed in terms of risks and benefits for the pregnant patient given the self-limited and fully resolving pathology. Surgical decompression to reduce the intramedullary pressure caused by bone marrow edema has been demonstrated in case reports, although there is debate on the utility of this procedure and its potential to increase the fracture risk of already osteoporotic bone (14,18). Oral and intravenous bisphosphonate therapies have shown rapid efficacy in resolving TOH (19,20).
Ringe et al. (21) found that administering an initial 4-mg intravenous dose of ibandronate with an optional second 2-mg dose at 3 months decreased visual analog pain scales by an average of 94.3% (n = 12). There also was a decrease from 10.1% to 2.6% difference in bone mineral density from the affected hip to the unaffected hip at 6-month follow-up. The use of bisphosphonate to treat TOH in a pregnant woman is debated because of the confirmed deposit in fetal bone due to transplacental pass. However, cases exist that show the benefit of this treatment without causing fetal harm (22). Potential alternatives to bisphosphonate therapy include the use of calcitonin (23,24) or teriparatide (25) therapy. Case reports have demonstrated that both of these treatments are potentially effective in resolving TOH, but there is a general lack of evidence that they are superior to conservative therapy alone.
TOP can result in devastating debilitation for an otherwise young healthy pregnant female. TOP is often difficult to diagnose because of the need for advanced imaging and the nonspecific nature of its clinical presentation. Conservative treatment may not be sufficient for TOP, and the risks versus benefits for both the mother and fetus must be discussed prior to using second-line treatments. Health care providers must have a high level of suspicion for this acute cause of pain. With greater recognition and reporting of this pathology, there can be a more robust establishment of guidelines for the prevention, diagnosis, and treatment of TOP.
The authors declare no conflict of interest and do not have any financial disclosures.
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