Prevalence of Low Serum Alkaline Phosphatase and Hypophosphatasia in Adult Patients with Atypical Femur Fractures.

Hypophosphatasia (HPP) is a rare genetic disorder characterized by low serum alkaline phosphatase (ALP), its manifestations may include atypical femoral fractures (AFF). However, the prevalence of low serum ALP and HPP in patients with AFF remains unknown. We retrospectively analyzed ALP levels and clinical manifestations compatible with HPP in 72 adult patients with confirmed AFF by chart review. ALP values were compared with those of a control group of patients with prior proximal femoral fracture during antiresorptive treatment (n = 20). Among the AFF patients, 18 (25%) had at least one serum ALP value ≤ 40 IU/L, although in all but one case, at least one ALP value > 40 IU/L was also detected at another time point. Most low ALP values were associated with antiresorptive treatment (P = 0.049) and lowest levels of ALP did not differ between the AFF and the control groups (P = 0.129). However, low ALP values among AFF patients were associated with a higher rate of bilateral AFF (50% vs 22%, P = 0.025), metatarsal fracture (33% vs 7%, P = 0.006), and with trends for more frequent use of glucocorticoid (22% vs 8%, P = 0.089) and proton pump inhibitor (61% vs 44%, P = 0.220). In one AFF patient with low ALP and clinical suspicion of HPP, a rare pathogenic heterozygous variant of the ALPL gene was identified. In conclusion, low ALP values are common among subjects with AFF and mainly related to concomitant antiresorptive medication. Hence, low serum ALP has low specificity for HPP among AFF patients.

Functional and clinical outcomes of patients aged younger and older than 85 years after rehabilitation post-hip fracture surgery in a co-managed orthogeriatric unit.

AIM: Literature investigating rehabilitation outcomes after hip surgery among individuals aged ≥85 years is sparse. We compared the characteristics and outcomes of patients aged under and over 85 years, and assessed factors potentially associated with rehabilitation success as described by the Barthel Index (BI). METHODS: From 2011 to 2014, we prospectively enrolled 328 patients (n = 152 aged <85 years, n = 176 aged ≥85 years) admitted to an orthogeriatric unit (Sondrio, Italy) with a diagnosis of hip fracture requiring surgical treatment. We excluded patients who were being treated conservatively. Outcomes included absolute functional gain (AFG; BI at discharge - BI on admission), rehabilitation effectiveness index (AFG / length of stay) and postoperative complications. RESULTS: Older patients were more functionally (mean BI on admission: 11.7 ± 9.6 vs 16.4 ± 12.2, P < 0.001) and cognitively impaired than their younger counterparts (34.1% vs 18.4%, P < 0.001). Surgery time (1.9 ± 1.2 vs 2.3 ±1.3 days, P = 0.008) and length of stay were shorter for older patients (5.7 ± 2.1 vs 6.6 ± 2.4 days, P < 0.001). There were no differences in terms of complications. Patients aged <85 years showed better functional outcomes (BI, AFG, REI) at discharge than patients aged ≥85 years (mean AFG: 38.2 ± 24.2 vs 26.1 ± 22.0, P < 0.001). BI on admission (OR 1.05, 95% CI 1.02-1.08) and cognitive impairment (OR 0.58, 95% CI 0.34-0.98) were independently associated with rehabilitation outcomes, regardless of chronological age. CONCLUSIONS: Both groups (aged <85 and ≥85 years) showed a significant functional improvement at discharge. Older patients show a residual ability to recover after surgery. A high rehabilitation efficiency - regardless of age - should be pursued even for the oldest old patients experiencing hip fracture. Geriatr Gerontol Int 2018; 18: 1194-1199.

[Hypophosphatasia]. / Hypophosphatasie de l'adulte.

Hypophosphatasia (HPP) is an inborn metabolic bone disorder caused by loss-of-function mutations in the gene encoding tissue nonspecific alkaline phosphatase (TNSALP). The adult form can be mistaken with common osteoporosis and/or present recurrent metatarsal fractures, skeletal and muscular pain. Subtrochanteric femoral pseudofractures resembling bisphosphonate-associated atypical femoral fractures can also be present, and Bps are therefore contraindicated in HPP. Early tooth loss and renal calcifications can orient towards the diagnosis. The diagnosis is based on low serum ALP levels (< 40 U/L) and high ALP substrate levels, such as vitamin B6 (pyridoxin), eventually on genetic testing. Recent development of an enzyme replacement therapy offers new therapeutic perspectives in severe cases.

L'hypophosphatasie (HPP) est une maladie rare due à une perte de fonction du gène de la phosphatase alcaline (ALP). La forme adulte peut être facilement confondue avec une ostéoporose banale. Elle se manifeste aussi par des fractures de stress, des douleurs osseuses et des myalgies. Des pseudofractures des fémurs proximaux ressemblent aux fractures atypiques par bisphosphonates, qui sont donc contre-indiqués en cas d'HPP. La perte précoce des dents et des calcifications rénales peuvent mettre sur la piste d'une HPP. Le diagnostic est fondé sur l'histoire clinique et des valeurs basses d'ALP (< 40 U/l), hautes de ses substrats, notamment la vitamine B6, et finalement sur les tests génétiques. Le développement récent d'un substitut enzymatique offre de nouvelles perspectives thérapeutiques dans les cas sévères.

Effects of strontium ranelate on bone mass and bone turnover in women with thalassemia major-related osteoporosis.

Subjects affected by thalassemia major (TM) often have reduced bone mass and increased fracture risk. Strontium ranelate (SrR) is an effective treatment for postmenopausal and male osteoporosis. To date, no data exist on the use of SrR in the treatment of TM-related osteoporosis. Our aim was to evaluate the effects of SrR on bone mineral density (BMD), bone turnover markers and inhibitors of Wnt signaling (sclerostin and DKK-1). Twenty-four TM osteoporotic women were randomized to receive daily SrR 2 g or placebo in addition to calcium carbonate (1,000 mg) and vitamin D (800 IU). BMD at the lumbar spine and femoral neck, bone turnover markers (C-terminal telopeptide of procollagen type I [CTX], bone-specific alkaline phosphatase [BSAP]) and insulin-like growth factor-1 (IGF-1), sclerostin and DKK-1 were assessed at baseline and after 24 months. Back pain was measured by visual analog scale (VAS) every 6 months. After 24 months, TM women treated with SrR had increased their spine BMD values in comparison to baseline (p < 0.05). Moreover, they also exhibited a reduction of CTX and sclerostin levels (but not DKK-1) and exhibited an increase of BSAP and IGF-1 (p < 0.05); however, no significant changes were observed in the placebo group. In the SrR group, a reduction of back pain was observed after 18 months in comparison to baseline (p < 0.05) and after 24 months in comparison to placebo (p < 0.05). Our study reports for the first time the effects of SrR in the treatment of TM-related osteoporosis. SrR treatment improved BMD and normalized bone turnover markers, as well as lowering sclerostin serum levels.