Value of Intraoperative Parathyroid Hormone Monitoring

Background Routine use of intraoperative parathyroid hormone (IOPTH) has been challenged in both unilateral/limited (LE) and bilateral exploration (BE). To investigate this, we assessed the usefulness of IOPTH in surgical management of primary hyperparathyroidism and parathyroid carcinoma (PC). Methods Between 1998 and 2006, 1133 patients were explored for hyperparathyroidism: 185 LE, 743 BE with IOPTH, 95 BE without IOPTH, 110 reoperations, and 4 PCs. IOPTH patterns were correlated with parathyroid pathology (single adenoma [SA] or multigland disease [MGD]) and operative success. Results In LE, IOPTH returned to normal in 78% of patients; all patients had SA, and 99% were cured at a mean ± SEM of 1.2 ± .24 years; 22% of LE patients (n = 41) whose IOPTH did not return to normal were converted to BE, and all had MGD. BE with and without IOPTH was equally successful 97% and 98% (P = NS) of the time, respectively. In BE in which IOPTH did not return to normal, 9% of patients remained hypercalcemic; tumor distribution mirrored other BE patients (75% SA, 25% MGD). In reoperations, a normal final IOPTH correlated with cure in 99%; otherwise, 59% had persistent disease. Differential bilateral internal jugular vein IOPTH sampling lateralized disease in 77% of reoperations. Conclusions IOPTH is an important adjunct for successful LE by identifying the presence of MGD and avoiding operative failure. IOPTH adds little to BE; however, final IOPTH values may predict persistent disease in BE, reoperations, and PCs.     

Intraoperative Parathyroid Hormone Monitoring in Patients with Recognized Multiglandular Primary Hyperparathyroidism

Background  

Intraoperative parathyroid hormone (IOPTH) monitoring reliably predicts cure of primary hyperparathyroidism (PHPT) due to single-gland disease. However, its utility in PHPT caused by multiple-gland disease (MGD) is still debated, for both detection and prediction of adequate resection. Our hypothesis is that once MGD is encountered during an operation, more stringent criteria for determining adequate resection can improve cure rates.     

Unexpected Results Using Rapid Intraoperative Parathyroid Hormone Monitoring during Parathyroidectomy for Primary Hyperparathyroidism

Rapid intraoperative parathyroid hormone (RIOPTH) monitoring predicts complete removal of all hypersecreting tissue by means of a significant parathyroid hormone (PTH) decrease. In this study we have tried to provide an explanation for some unexpected results of RIOPTH monitoring observed during a series of 125 conventional parathyroidectomies for primary hyperthyroidism, discussing the possible consequences on the surgical strategy. Three main groups can be recognized: (1) spikes: a PTH increase 10 minutes after removal of the diseased gland was observed in three patients; (2) false-negative results: six patients showed an inadequate PTH decreases at 10 minutes, three of them resulting in cure at 20 minutes (all six patients were cured at follow-up); (3) false-positive results: five patients with multiglandular disease showed a PTH decrease to a cure level despite excision of one adenoma only (in two of these patients a 20-minute sample showed a PTH increase soon after manipulation of the second adenoma). We concluded that the spike, almost certainly a consequence of manipulating the adenoma, when detected should be considered the “true” baseline value. False-negative results are to some extent related to undetected spikes. The assay used for RIOPTH determination and PTH half-life variability may also play a role. A false-negative result usually prolongs the surgical time. False-positive results are usually related to a double adenoma, one functionally prevailing over the other. Because in our experience manipulation of the second adenoma brought a PTH increase detected with RIOPTH monitoring, we believe that the second adenoma should be excised.     

Intraoperative Secretion of Intact Parathyroid Hormone and Amino-Terminal Parathyroid Hormone Fragments from Normal Parathyroid Glands Associated with Solitary Parathyroid Adenoma

p < 0.05 for both). Because the reduction was more pronounced for i-PTH than for N-PTH, the N/i ratio increased from 0.54 ± 0.33 to 3.76 ± 1.62 ( p < 0.05). Furthermore, the levels of i-PTH and N-PTH were higher centrally than peripherally both before and after adenoma excision ( p < 0.05). The results therefore suggest that the secretion of i-PTH and N-PTH in the remaining normal-size parathyroid glands is not completely suppressed. Furthermore, in these parathyroid glands the secretion of amino-terminal PTH fragments is relatively predominant when compared to the release of the intact PTH. The findings underscore the importance of the N-terminal PTH fragment for maintaining calcium homeostasis during the early postoperative period after surgery for pHPT and may explain the rarity of prolonged hypocalcemia after parathyroidectomy.     

New Point-of-care Intraoperative Parathyroid Hormone Assay for Intraoperative Guidance in Parathyroidectomy

The use of the intraoperative parathyroid hormone assay (QPTH) to guide a limited parathyroidectomy in patients with sporadic primary hyperparathyroidism (SPHPT) is well established. The advantage of having this assay performed in the operating room is immediate feedback for (1) confirming the complete excision of all hyperfunctioning parathyroid(s); (2) differential jugular venous sampling for localization; and (3) diagnosing suspected tissue without histopathology. For these reasons, the reliability of the hormone measurement and a short assay turnaround time are essential for surgical guidance. We report our experience using a new "point-of-care" assay for intact parathyroid hormone (iPTH). A new two-site chemiluminescent immunometric assay was used. The antibodies are inside a microtiter well, where the iPTH is measured by a strip luminometer after incubation for 5 minutes. Sixteen frozen samples were measured simultaneously using the traditional iPTH assay and this new assay for comparison. Fifty-one patients with SPHPT underwent parathyroidectomy guided by this new assay. The criteria used to predict postoperative normocalcemia was a drop in the hormone level of ≤ 50% from the highest preincision or preexcision levels at 10 minutes after excision of all hypersecreting gland(s). The correlation between the traditional and new assays was 0.98. The assay predicted the postoperative calcium levels in all patients except one (false negative-delayed drop). The assay turnaround time was 8 minutes. This new point-of-care assay is reliable for predicting postoperative calcium levels when used with the described criteria. It has advantages over the traditional assay in that it is faster and easier to perform.     

Intra-operative Parathyroid Hormone Monitoring in Patients with Parathyroid Cancer

Background Intra-operative parathyroid hormone (PTH) monitoring (IPM) is 97% accurate in predicting postoperative eucalcemia in sporadic primary hyperparathyroidism (SPHPT). However, its usefulness in parathyroid cancer has not been demonstrated. This study reports IPM accuracy during surgical resections for parathyroid cancer. Methods Eight of 556 consecutive patients with SPHPT underwent parathyroidectomy using IPM and had parathyroid cancer. Operative success was defined as eucalcemia > six months and operative failure/persistent cancer as hypercalcemia within six months of parathyroidectomy. The IPM criterion for operative success was defined as a >50% decrease of peripheral PTH levels from the highest either pre-incision or pre-excision values, 10 minutes after resection. Results In eight patients, 11 operations were performed. Ten operations (91%) resulted in >50% intra-operative PTH decrease. However, in only seven (70%) of these resections, eucalcemia was achieved for >6 months with five of these seven (71%) procedures being initial en bloc resections. The remaining 3/10 (30%) operations with >50% intra-operative PTH decrease resulted in operative failures. In the last operation, intraoperative parathormone monitoring (IPM) correctly predicted operative failure. IPM sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy in predicting outcome were 100, 40, 70, 100, and 75%, respectively. Conclusions IPM with the criterion of >50% PTH drop from the highest level is less accurate in predicting operative success in parathyroid cancer when compared to SPHPT. A >50% intra-operative PTH level decrease in patients with parathyroid cancer, particularly in reoperative cases, is less predictive of complete resection. The initial recognition of this disease followed by proper resection remains essential in the treatment of parathyroid cancer.     

The Value of Intraoperative Parathyroid Hormone Monitoring in Localized Primary Hyperparathyroidism: A Cost Analysis

Background  

Minimally invasive parathyroidectomy (MIP) is the preferred approach to primary hyperparathyroidism (PHPT) when a single adenoma can be localized preoperatively. The added value of intraoperative parathyroid hormone (IOPTH) monitoring remains debated because its ability to prevent failed parathyroidectomy due to unrecognized multiple gland disease (MGD) must be balanced against assay-related costs. We used a decision tree and cost analysis model to examine IOPTH monitoring in localized PHPT.     

Focused Cervical Exploration for Primary Hyperparathyroidism without Intraoperative Parathyroid Hormone Monitoring or Use of the Gamma Probe

Selected patients with primary hyperparathyroidism (pHPT) who have a positive preoperative sestamibi scan can be managed safely and successfully with a focused cervical exploration without either adjuvant intraoperative parathyroid hormone (PTH) monitoring or use of a gamma probe. This article reports a retrospective analysis of a consecutive series of patients surgically treated at a tertiary referral center. From August 1998 to August 2002, 100 patients (68 women, 32 men; mean age 63 years [range: 29–89 years]) underwent a focused cervical approach without intraoperative PTH monitoring or use of the gamma probe after perioperative sestamibi injection. The study group comprised 9% of all patients (n = 1063) undergoing cervical exploration for pHPT during the study period. Ninety patients underwent an initial exploration, and 10 others underwent repeat cervical exploration following prior parathyroid (n = 7) or thyroid (n = 3) operation. Sestamibi scanning correlated with one enlarged parathyroid gland in all patients. Other enlarged glands were, however, not demonstrated in three patients (true positive = 97%; false negative = 3%). The single enlarged glands excised in all patients had a mean weight of 795 mg (range: 90–3640) and were histologically compatible with an adenoma. Postoperatively, 97% of patients were eucalcemic. Three patients remained hypercalcemic (3%). Of the three patients with persistent hypercalcemia, one underwent successful re-exploration with excision of a 500 mg second adenoma, whereas the other two patients (with confirmed familial HPT) remained hypercalcemic. Mean hospitalization was 0.5 days (range: 0–3 days). There was no operative mortality. No patients had permanent hypocalcemia. Postoperative morbidity occurred in three patients: two self-limiting cervical hematomas and one permanent vocal cord paralysis. Selected patients with pHPT due to single-gland disease and an unequivocally positive preoperative sestamibi scan can safely and successfully be managed with a focused unilateral cervical exploration without either intraoperative PTH monitoring or use of the gamma probe. Further experience with this surgical approach seems warranted to determine the overall cure rate, operative morbidity, and the sensitivity and specificity of preoperative localization studies.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden, June 14-17, 2004.     

Intraoperative Parathyroid Aspiration and Parathyroid Hormone Assay as an Alternative to Frozen Section for Tissue Identification

Most people would agree that successful parathyroidectomy depends on two important variables: the surgeon's recognition and excision of the abnormal parathyroid gland(s) and the pathologist's confirmation that the removed tissue is parathyroid tissue. Frozen section is usually employed to confirm the identity of parathyroid tissue, but occasionally confirmation cannot be made without a permanent section, as with intrathyroidal glands. This study proposes a new method of expeditious and easy confirmation of parathyroid tissue utilizing the immunoassay for quick measurement of intraoperative parathyroid hormone (IOPTH). By directly aspirating the suspected adenoma, the assay becomes a rapid diagnostic tool that can be used as an alternative to frozen section. In cases where the surgeon is already planning to employ the assay, the elimination of frozen section is cost-effective. Intraoperative aspiration of histologically confirmed parathyroid adenomas was performed on 12 consecutive patients undergoing parathyroid surgery. Parathyroid glands were aspirated with a 22-gauge syringe after gland excision. Aspirates were placed in 1 to 3 ml of buffered saline. A similar process was performed on 12 thyroid controls. Specimens were centrifuged, aliquotted, and stored at −70°C. The parathyroid hormone value was analyzed electively by rapid assay and the values recorded. For all parathyroid aspirates, the rapid assay value was > 1500 pg/ml, exceeding the uppermost limit of the diagnostic chart. Values for thyroid aspirates ranged from 58 to 85 pg/ml (mean 75.7 pg/ml). In all cases tissue confirmation was achieved with permanent section. Values were 100% sensitive and specific. Measurement of PTH from intraoperative aspiration of suspected parathyroid adenomas is clinically useful in patients for whom frozen section would routinely be employed. Values > 1500 pg/ml secure the tissue diagnosis. There is no additional cost in cases where IOPTH monitoring is already being utilized to confirm cure. The elimination of frozen section could be cost-effective and, for some institutions, actually decrease the operating time as the IOPTH assay takes only 15 minutes. PTH assay is an accurate diagnostic technique and to date is 100% sensitive and specific for differentiating between parathyroid tumors and thyroid nodules.     

Operative Failure in Minimally Invasive Parathyroidectomy Utilizing an Intraoperative Parathyroid Hormone Assay

Background

Minimally invasive parathyroidectomy (MIP) is a targeted operation to cure primary hyperparathyroidism utilizing intraoperative parathyroid hormone monitoring (IOPTH). The purpose of this study was to quantify the operative failure of MIP.

Methods

Utilizing institutional parathyroid surgery database, demographic, operative, and biochemical data were analyzed for successful and failed MIP. Operative failure was defined as <6 months of eucalcemia after operation.

Results

Five hundred thirty-eight patients (96.6 %) had successful MIP with mean follow-up of 13 months, and 19 (3.4 %) had operative failure. The major cause of operative failure (11 of 19) was the result of surgeons’ inability to identify all abnormal parathyroid glands. The remaining eight operative failures were the result of falsely positive IOPTH results. Eleven of 19 patients whose MIP had failed underwent a second parathyroid surgery. All but one of these patients achieved operative success, and 9 patients had missed multigland disease. Only 46 (8.3 %) of 557 patients had conversion to bilateral cervical exploration (BCE). Eighty percent of patients had more than 70 % IOPTH decrease, and all had successful operations. Patients with a marginal IOPTH decrease (50–59 %) had a treatment failure rate of 20 %.

Conclusions

The most common cause of operative failure in MIP utilizing IOPTH was the result of surgeons’ failure to identify all abnormal parathyroid glands. Falsely positive IOPTH is rare, and a targeted MIP utilizing IOPTH can achieve an excellent operative success rate without routine BCE. Selective BCE on patients with marginal IOPTH decrease may improve surgical outcome.     

Intraoperative Parathyroid Hormone Assay Remains Predictive of Cure in Renal Impairment in Patients with Single Parathyroid Adenomas

Background

Parathyroid hormone (PTH) has a short half-life and is cleared by the liver and kidneys. This study examined whether declining estimated glomerular filtration rate (eGFR) affects application of the Miami criterion for intraoperative PTH (ioPTH) decline during parathyroidectomy for primary hyperparathyroidism (pHPT).

Methods

A retrospective review of consecutive patients undergoes parathyroidectomy for pHPT. Patients with multi-gland disease, without ioPTH, failure-to-cure and those <18 years were excluded. Baseline demographics, pre-operative PTH, ioPTH and 6-month follow-up data were available. Patients were categorised into normal or chronic kidney disease (CKD stage 2–5) based on pre-operative eGFR. Nonparametric data were compared using Mann–Whitney U test/Kruskal–Wallis test. The primary outcome measure was to assess whether CKD-affected ioPTH decline in parathyroidectomy for pHPT.

Results

A total of 476 patients were included [75.4% women; median age 63.8 years (18–92)]. CKD was present in 362 (76%) (CKD2:289; CKD3:66; CKD4/5:7). Increasing CKD stage was associated with advancing age [normal 53 years (41–61); CKD2 65 (57–73); CKD3 73.5 (66–78); CKD4/5 74(63–81); p < 0.001] and higher pre-operative PTH [16.6 pmol/L (11.1–22.9); 13.1 (10.4–17.7); 22.6 (13.8–33.7); 33.8(12.4–41.7); p < 0.001]. Baseline and post-excision ioPTH were significantly higher in those with CKD4/5 (p < 0.05). The Miami criterion was met in all patients, but median fall in ioPTH at 10-min varied between groups [normal:0.78 (0.71–0.82); CKD2:0.76 (0.69–0.83); CKD3:0.75 (0.69–0.82); CKD4/5:0.69 (0.61–0.70); p = 0.048)]. It was significantly lower in those with CKD4/5 compared with the remainder of patients [0.69 (0.61–0.70) vs. 0.76 (0.70–0.82); p = 0.008].

Conclusions

Although the reduction in ioPTH after successful parathyroidectomy is lower in severe CKD, the Miami criterion remains predictive of cure. Differences in absolute levels of PTH and tumour weight suggest that renal HPT may be a confounding factor.

     

Utility of Intraoperative Parathyroid Hormone Monitoring in Patients with Multiple Endocrine Neoplasia Type 1-Associated Primary Hyperparathyroidism Undergoing Initial Parathyroidectomy

Background

Intraoperative parathyroid hormone monitoring (IOPTH) is a widely used adjunct for primary hyperparathyroidism (pHPT). However, the benefit of IOPTH in familial pHPT, such as in multiple endocrine neoplasia type I (MEN1), remains unclear.

Methods

We performed a retrospective analysis of 52 patients with MEN1-associated pHPT undergoing initial parathyroidectomy with IOPTH monitoring at our institution. Parathyroid hormone (PTH) levels were measured before skin incision and 10 min after resection of the last parathyroid gland. Variables analyzed included percent drop of PTH from baseline and the final PTH level compared to the normal reference range (RR).

Results

A total of 52 patients underwent initial subtotal parathyroidectomy with IOPTH. An IOPTH decrease cutoff of ≥75 % from baseline had the highest biochemical cure rate (87 %). In the remaining 13 % who met this cutoff, all had persistent pHPT, with ≥90 % drop of PTH from baseline. The remaining patients, who did not meet the ≥75 % cutoff, were cured. Follow-up was available for three of four patients with final IOPTH levels above the RR: one had persistent pHPT, two had hypoparathyroidism (50 %). When a postresection PTH level was within the RR, 88 % of patients were cured. While considered cured from pHPT, 7 % of patients in this group developed permanent hypoparathyroidism. When the final PTH level dropped below the RR, 28 % developed permanent hypoparathyroidism.

Conclusions

A cutoff in IOPTH decrease of ≥75 % from baseline has the highest biochemically cure rate in patients with pHPT associated with MEN1. However, a 75 % cutoff in IOPTH decrease does not exclude persistent pHPT. The absolute IOPTH value does not accurately predict postoperative hypoparathyroidism.     

Impact of Intraoperative Parathyroid Hormone Levels on Surgical Results in Patients with Renal Hyperparathyroidism

The aim of our study was to evaluate the impact of intraoperative parathyroid hormone (PTH) measurement on surgical results in patients with renal hyperparathyroidism (HPT). From December 1999 to February 2004, a series of 95 consecutive patients underwent total parathyroidectomy and intraoperative PTH measurement for renal HPT. Intraoperative PTH was measured before and 15 minutes after parathyroidectomy with the Immulite DPC assay for intact PTH. The median PTH levels before surgery were 133.0 pmol/L, which declined to 5.9 pmol/L at the end of the operation. At follow-up, 91 of 95 (96%) patients presented with normal calcium levels. Persistent renal HPT was seen in three patients, and recurrent HPT was diagnosed in another. In 99% of the patients the intraoperative PTH levels declined more than 50% and in 73% the PTH decay was more than 90%. In 64% of the patients PTH levels dropped into the normal range (< 7.6 pmol/L). Altogether, 97% of the patients with an intraoperative PTH decrease of more than 90% presented with normal PTH levels postoperatively (p = 0.0237), as did all of the patients whose intraoperative PTH dropped into the normal range (p = 0.0432). Intraoperative PTH measurement with a decrease in intraoperative PTH of at least 90% is highly predictive of successful parathyroidectomy and normalization of postoperative calcium and PTH levels.     

Applicability of Intraoperative Parathyroid Hormone Assay During Total Thyroidectomy as a Guide for the Surgeon to Selective Parathyroid Tissue Autotransplantation

Background Intraoperative parathyroid hormone assay (IOPTH) has been suggested to have value in predicting the development of postoperative hypoparathyroidism after thyroid surgery. IOPTH has been validated in identification of patients at risk of postoperative hypocalcemia requiring early onset of calcium supplementation therapy and in improving selection of patients eligible for a safe early discharge. However, the value of IOPTH has not been assessed in a randomized study as a guide for the surgeon to parathyroid tissue autotransplantation (PA). The objective of this study was to evaluate the applicability of IOPTH in guiding the surgeon to selective parathyroid tissue autotransplantation during total thyroidectomy (TT). Methods Between January 2005 and December 2005, 340 patients qualified for total thyroidectomy (TT) who met the inclusion criteria were randomized to two equal-sized groups (n = 170): group A, in which elective PA of at least one parathyroid gland was performed in all cases without IOPTH as a guide; and group B, in which selective IOPTH-guided PA was performed, if only the iPTH plasma level was <10 ng/L at 10–20 min after TT (before skin closure). The standard technique of PA consisting of implanting the parathyroid tissue into 10–20 sternocleidomastoid muscle pockets was used in both groups. IOPTH measurements were performed by the STAT-Intraoperative-iPTH-Assay. Serum calcium was routinely monitored at 4, 12, 24, 48, and 72 hr postoperatively. The incidence and severity of hypocalcemia and related symptoms were matched with the IOPTH results. On follow-up, serum calcium and plasma iPTH values were measured at 1, 3, and 6 months postoperatively. The primary end point was the success rate in preventing permanent postoperative hypoparathyroidism. The secondary end point was the use of postoperative medication for transient hypocalcemic symptoms. Results Twenty-one group B patients (12.3%) had plasma iPTH levels <10 ng/L at 10–20 min after TT (before skin closure) and they underwent selective IOPTH-guided PA. None of the patients from both groups experienced permanent postoperative hypoparathyroidism. Transient postoperative hypocalcemia occurred in 22.3% vs. 11.2% of patients (group A vs. B, respectively; p < 0.05). The mean cumulated serum calcium values were significantly lower for group A vs. group B patients within the entire 3-month period after TT (2.12 ± 0.09 mmol/L vs. 2.27 ± 0.05 mmol/L, respectively; p < 0.001). The mean oral calcium supplementation was significantly higher for group A vs. group B patients during the 3 months after TT (2.7 ± 0.9 g/day vs. 0.9 ± 0.4 g/day, respectively; p < 0.001). Conclusions IOPTH offers valuable information during TT, correctly identifying patients at risk of postoperative hypocalcemia. Selective IOPTH-guided PA in patients with plasma iPTH levels <10 ng/L at 10–20 min after TT reduces the risk of permanent postoperative hypoparathyroidism to zero, and this approach seems to be as effective as elective PA of at least one parathyroid gland without IOPTH guidance. Moreover, selective IOPTH-guided PA significantly decreases the incidence of transient postoperative hypoparathyroidism and the need for calcium supplementation therapy compared with elective PA without IOPTH. Presented at the 42^nd World Congress of Surgery, Montreal, Canada, August 26 to 30, 2007.     

Minimal Benefit to Subsequent Intraoperative Parathyroid Hormone Testing After All Four Glands Have Been Identified

Background

Modern tools, such as intraoperative parathyroid hormone (IoPTH) assay, reduce operative time and extent of parathyroidectomy. However, the utility of a subsequent final set of IoPTH after all four glands are visualized remains questionable. This study was designed to determine the added value of IoPTH assay following parathyroidectomy with four-gland visualization in patients with primary hyperparathyroidism (PHPT).

Methods

A retrospective review of patients who underwent parathyroidectomy for PHPT between July 2001 and February 2012 by two experienced endocrine surgeons was performed. Included were patients with operative reports indicating that all four parathyroid glands were identified. Following four-gland visualization a subsequent final set of IoPTH was measured to confirm cure. Cure was defined as at least 50 % fall by 5, 10, or 15 min postexcision compared with preincision levels.

Results

Of 1,838 patients that underwent parathyroidectomy, four glands were visualized in 238 cases (13 %). Of those patients meeting inclusion criteria with four glands visualized, the final set of IoPTH fell to cure criteria in 235 patients (98 %). An inadequate drop was documented in three (2 %) patients all of which were found to have multigland disease. Only in one patient (0.4 %) was a fifth parathyroid gland identified and resected. In all three cases, the subsequent final IoPTH did not affect the ultimate outcome or cure rate.

Conclusions

When experienced surgeons visualize all four parathyroid glands, drawing a subsequent final set of IoPTH rarely changes the operative course and therefore serves a limited role.     

25-Hydroxyvitamin D Status Does Not Affect Intraoperative Parathyroid Hormone Dynamics in Patients with Primary Hyperparathyroidism

Background  

Deficiency of 25-hydroxyvitamin D (25OHD) is a stimulus for the secretion of parathyroid hormone (PTH). During surgery for primary hyperparathyroidism, 25OHD deficiency may artificially elevate PTH, decreasing the sensitivity of intraoperative PTH (ioPTH) measurements.     

Parathyroid Hormone and Bone Healing

Fracture healing is a complex process, and a significant number of fractures are complicated by impaired healing and non-union. Impaired healing is prevalent in certain risk groups, such as the elderly, osteoporotics, people with malnutrition, and women after menopause. Currently, no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial in the treatment of fractures and could thus be a potentially new treatment option for induction of fracture healing in humans. Furthermore, fractures in animals with experimental conditions of impaired healing such as aging, estrogen withdrawal, and malnutrition can heal in an expedited manner after PTH treatment. Interestingly, fractures occurring at both cancellous and cortical sites can be treated successfully, indicating that both osteoporotic and nonosteoporotic fractures can be the target of PTH-induced healing. Finally, the data suggest that PTH partly prevents the delay in fracture healing caused by aging. Recently, the first randomized, controlled clinical trial investigating the effect of PTH on fracture healing was published, indicating a possible clinical benefit of PTH treatment in inducing fracture healing. The aim of this article is therefore to review the evidence for the potential of PTH in bone healing, including the underlying mechanisms for this, and to provide recommendations for the clinical testing and use of PTH in the treatment of impaired fracture healing in humans.