Muriel S. Parisi

Effect of intravenous pamidronate on bone markers and local bone mineral density in fibrous dysplasia

Bisphosphonates have proven to be effective in patients with fibrous dysplasia of the bone (FD) as shown by their effect on bone pain, markers of bone turnover, or radiological changes. The aim of this study was to evaluate the usefulness of measuring bone mineral density (BMD) of affected bones to assess the efficacy of bisphosphonate treatment. Seven patients (mean age 26 years) received courses of 180 mg intravenous infusion of pamidronate every 6 months (60 mg/day during 3 days). Clinical symptoms, serum alkaline phosphatase, and urinary C-terminal cross-linking telopeptide of type I collagen were assessed every 3 months. BMD of total skeleton and X-rays of FD areas (FDa) were performed at baseline and at 12 months. BMD of FDa was compared with the contralateral side (CL) using the region of interest program on the total skeleton scan. BMD of total skeleton was normal at baseline. Average BMD of FDa was -11.4% compared with CL, a significantly greater difference than that observed between the left and right sides in healthy controls, -0.7% (P < 0.02). At 12 months bone pain diminished in all patients. Bone turnover markers decreased. Mean total skeleton BMD increased 3.3% (P < 0.02). Subregions of the total skeleton scan presenting FD lesions augmented: arms +9.6% (P < 0.02), legs +4.2%, and pelvis +3.5% (P < 0.05). The increase in mean BMD of FDa was +6.8% compared with +2.6% in CL. No changes were observed on the X-ray. These results indicate that simultaneous determination of markers of bone turnover and BMD of FDa is useful in short-term follow-up to determine the efficacy of intravenous pamidronate.

Bone Mineral Density Response to Long-Term Bisphosphonate Therapy in Fibrous Dysplasia

Fibrous dysplasia of bone is a rare disease related to a genetic mutation in which bone formation at osseous sites is altered. In the last few years, bisphosphonates have become one of the choice drugs to treat this disease. A 26-yr-old woman presented after 6 wk of spontaneous right leg pain owing to a fissure fracture of the right femoral neck. She reported precocious puberty at the age of 2, with diagnosis of McCune-Albright syndrome. Radioisotope bone scanning, radiographic, biochemical, and densitometric studies were performed. Treatment with bisphosphonates was started because bone turnover biochemical markers were abnormal. Oral olpadronate followed by iv pamidronate substantially decreased bone resorption. Bone mineral density (BMD) of total skeleton and subareas was assessed by dual X-ray absorptiometry (DXA) throughout the 5 yr of treatment. At the end of this period, BMD of the total skeleton had increased 6.2%. However, BMD of the areas most affected by fibrous dysplasia, the legs and pelvis, had increased 12.7 and 11%, respectively. Region of interest analysis of individual bones of the legs performed with the total skeleton scan revealed that BMD of the areas most affected by fibrous dysplasia was lower than that of the less affected contralateral bones. During the first 3 yr, treatment with bisphosphonates substantially increased BMD of the right femur and tibia (22 and 28%, respectively). After that, values seemed to stabilize. DXA evaluation of the total skeleton and its subareas was useful to evaluate the efficacy of bisphosphonate treatment. Moreover, the plateau observed in BMD values after 3 yr of treatment suggests that treatment could have been discontinued when the densitometric values stabilized.

Long-Term Pamidronate Treatment of Polyostotic Fibrous Dysplasia of Bone: A Case Series in Young Adults

BACKGROUND Limited information is available about long-term pamidronate treatment in adults with fibrous dysplasia (FD) of bone. OBJECTIVE The aim of this case series was to report the clinical outcomes and the biochemical and densitometric findings in a group of young adult patients with polyostotic FD treated for ≥3 years with IV pamidronate. METHODS Pamidronate was administered every 6 months (60 mg/d for 3 days) for 2 years. Thereafter, treatment was individualized. Pamidronate was administered at shorter or longer intervals based on response. Bone pain, radiography, serum bone alkaline phosphatase (BALP) activity, and urinary C-terminal cross-linking telopep-tide of type I collagen (CTX-I) concentration were assessed for a mean of 7 years. Bone mineral density (BMD) of FD areas (FDas) and contralateral areas (CLas) were measured at baseline and at 12 and 24 months. Data were collected prospectively. RESULTS Seven patients (5 women, 2 men; mean [SD] age, 31.0 [7.2] years [range, 22-43 years]) were included in the study. Patients received IV pamidronate for a mean of 6.9 years (median, 7.1 years [range, 3.7-10.9 years]). Pamidronate was associated with a reduction in bone pain and a significant reduction in BALP in all patients at the end of follow-up (P < 0.02). The mean reduction from baseline in CTX-I concentration (measured in 3 patients) was 56%; this difference was not significant. Mean BMD values of FDas were significantly increased at 12 months (by 5.9%; P < 0.05) compared with baseline; but was not significantly increased at 24 months (7.3%), probably reflecting a higher dispersion of values due to individual responses to treatment. No significant changes were observed in CLa BMDs. Mean BMD of FDa had a numerically lower decrease of 15.3% compared with CLa at baseline; these decreases with pamidronate were 10.8% at 12 months (P = NS) and 9.3% at 24 months (P < 0.05). Refilling of osteolytic lesions was not observed. CONCLUSIONS These patients with FD of bone treated with IV pamidronate long term had improvement in bone pain and BMD. The effectiveness of individualized pamidronate administration in the long-term treatment of FD in adult patients should be investigated in blinded controlled trials.

Is ultrasound of bone relevant for corticosteroid-treated patients? A comparative study with bone densitometry measured by DEXA

Corticosteroid treatment diminishes bone mass and alters bone quality. The objective was to evaluate bone in corticosteroid-treated patients and controls and in fractured and non-fractured patients treated with corticosteroids using both X-ray densitometry (DEXA) and ultrasound. We evaluated 34 women aged 58 +/- 14 years (X +/- SD), who had been on long-term low dose prednisone therapy for at least 6 months, and who had never received specific treatment for osteoporosis. Bone mineral density of total skeleton (TS), lumbar spine (LS), femoral neck (FN), and vertebral morphometry (MXA) were measured by DEXA. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness were measured using an Achilles Plus system. Forty-two healthy women served as controls. Both densitometric and ultrasound parameters in the patients were significantly diminished compared with controls: TS: P < 0.002, LS: P < 0.025, FS: P < 0.005, Stiffness: P < 0.001, BUA: P < 0.002 and SOS: P < 0.002. The percentage of patients with a Z score below -2 was higher in Stiffness and BUA: 38% and 47%, respectively, compared with a range of 16-24% in the other parameters (P < 0.05 BUA vs. DEXA measurements). Eleven patients with previous bone fracture had values lower than the non-fractured patients, both according to DEXA and ultrasound measurements, but the difference was only significant for BUA (P < 0.02). BUA of the calcaneus was more effective in detecting the specific skeletal alterations and fracture risk of the group of patients receiving chronic corticosteroid treatment.

Resultados de una campaña de detección de población en riesgo para desarrollar osteoporosis y fracturas

Introduccion La osteoporosis es la enfermedad del metabolismo mineral mas frecuente del mundo occidental pero la mas subdiagnosticada y subtratada. Objetivo Detectar la poblacion en riesgo de sufrir osteoporosis y fracturas de cadera en sujetos de edad igual o superior a 50 anos. Materiales y metodos Se efectuaron charlas diarias organizadas por la Seccion Osteopatias Medicas y entrega de folletos informativos sobre osteoporosis a los concurrentes de la campana. Se realizaron densitometrias de radio (Lunar-Pixi Dual, DXA) en las participantes de 65 anos en adelante. De acuerdo a la edad, sexo y a la presencia de factores de riesgo (fracturas osteoporoticas, menopausia temprana y/o corticoterapia) los participantes se dividieron en: Grupo 1: mujeres entre 50 y 64 anos y hombres de edad igual o superior a 50 anos sin factores de riesgo; Grupo 2: igual que grupo 1, pero con factores de riesgo, y Grupo 3: mujeres de 65 anos o mas con o sin factores de riesgo. Resultados Participaron 1.305 personas de edad igual o superior a 50 anos (1.202 mujeres y 103 hombres). Grupo 1: total 364 (281 mujeres y 83 hombres); Grupo 2: total 315 (295 mujeres y 20 hombres), y Grupo 3: total 626 mujeres (52% del total de mujeres participantes). Ciento ochenta y cuatro participantes presentaron antecedentes de fracturas osteoporoticas. De estos, solo el 7% recibian o habian recibido tratamientos antirresortivos asociados a calico y/o vitamina D, el 14% solo calcio y el 5% calcio y vitamina D. El 84% de los participantes que realizaron densitometria de radio distal presentaban baja masa osea (T-score Conclusiones El 74% de las participantes con fracturas osteoporoticas previas no habian realizado o realizaban ningun tratamiento para osteoporosis y solo el 7% habia recibido medicacion antirresortiva. Mas de la mitad de las participantes mayores de 65 anos presentaron baja masa osea.